Method and apparatus for the measurement of autonomic function for the diagnosis and validation of patient treatments and outcomes

ABSTRACT

A pain measurement and diagnostic system (PMD) for bioanalytical analysis of pain matrix activity and the autonomic nervous system to diagnose and validate patient treatments, health status and outcomes to diagnose and validate patient treatments and outcomes. The PMD is implemented using medical devices for measuring and reporting objective measurements of pain through patient monitoring and analyzing related biological, psychological, social, environmental, and demographic factors that may contribute to and effect physiological outcomes for patients and through the analysis, improve diagnosis of pain, the evaluation of related disease states, and treatment options.

RELATED PATENT APPLICATION

This application is a divisional patent application of U.S. patentapplication Ser. No. 14/992,016 (now U.S. Pat. No. 10,376,203) filed onJan. 10, 2016 entitled METHOD AND APPARATUS FOR THE MEASUREMENT OFAUTONOMIC FUNCTION FOR THE DIAGNOSIS AND VALIDATION OF PATIENTTREATMENTS AND OUTCOMES that claims the benefit of U.S. ProvisionalPatent Application No. 62/101,992 filed Jan. 10, 2015 entitled METHODAND APPARATUS FOR THE MEASUREMENT OF AUTONOMIC FUNCTION which is herebyincorporated herein by reference in its entireties.

FIELD OF THE INVENTION

The present invention relates to a pain measurement and diagnosticsystem (PMD) for bioanalytical analysis of pain matrix activity and theautonomic nervous system to diagnose and validate patient treatments,health status and outcomes. The PMD is implemented using medical devicesfor measuring and reporting objective measurements of pain throughpatient monitoring and analyzing related biological, psychological,social, environmental, and demographic factors that may contribute toand effect physiological outcomes for patients and through the analysisimprove diagnosis of pain, evaluation of related disease states, andtreatment options.

BACKGROUND OF THE INVENTION

Currently there exists no valid and reliable method of objectivelyquantifying an individual's experience of pain (Younger J et al, PainOutcomes: A Brief Review of Instruments and Techniques. Curr PainHeadache Rep., 2009 February; 13(1):39-43). In the United States,approximately 100 million adults—more than the number affected by heartdisease, diabetes, and cancer combined—suffer from common chronic painconditions (Tsang, A et al, Common chronic pain conditions in developedand developing countries: Gender and age differences and comorbiditywith depression-anxiety disorders. Journal of Pain. 2008; 9(10):883-891)with an annual national economic cost associated with chronic painestimated to be $560-635 billion in 2011. The aging of the United Statespopulation means that a growing number of Americans will experience thediseases with which chronic pain is associated-diabetes, cardiovasculardisorders, arthritis, and cancer, among others (Cherry et al, Populationaging and the use of office-based physician services. NCHS Data Brief,No. 41. Hyattsville, Md.: National Center for Health Statistics).Increases in obesity will result in more orthopedic problems related tothe degradation of cartilage (Richettel et al., 2011). As a result,there will be a greater number of joint replacement surgeries, occurringin younger adult populations (Harms, S., R. Larson, A. E. Sahmoun, andJ. R. Beal. 2007. Obesity increases the likelihood of total jointreplacement surgery among younger adults. International Orthopaedics31(1):23-26; Changulani et al., 2008); resulting in associated acute andalso potentially chronic pain. Increases in disease states associatedwith pain will not only be experienced in the US. A UK Report from 2009,stated that, “chronic pain is two to three times more common now than itwas 40 years ago” (U.K. Department of Health. 2009. 150 years of thechief medical officer: On the state of public health. Annual Report.London: U.K. Department of Health; PAGE 34). There is no question thatpain, and other complex chronic disease states, are a major publichealth challenge. According to the Institute of Medicine's 2011study—Relieving Pain in America: A Blueprint for TransformingPrevention, Care, Education, and Research., pain is a uniquelyindividual and subjective experience that depends on a variety ofbiological, psychological, and social factors, and different populationgroups experience pain differentially (IOM (Institute of Medicine).2011. Relieving Pain in America: A Blueprint for TransformingPrevention, Care, Education, and Research. Washington, D.C.: TheNational Academies Press). Why one person suffers an injury and reportsmodest pain and another with a similar injury reports serious paindepends on many factors: genetic characteristics, general health statusand comorbidities, pain experiences from childhood on, the brain'sprocessing system, the emotional and cognitive context in which painoccurs, and cultural and social factors. Costly procedures often areperformed when other actions should be considered, such as prevention,counseling, and facilitation of self-care, which are common features ofsuccessful treatment. In addition, adequate pain treatment and follow-upmay be thwarted by a mix of uncertain diagnosis and societal stigmaconsciously or unconsciously applied to people reporting pain,particularly when they do not respond readily to treatment (IOM(Institute of Medicine). 2011. Relieving Pain in America: A Blueprintfor Transforming Prevention, Care, Education, and Research. Washington,D.C.: The National Academies Press). For these reasons, it is importantto develop an objective manner to measure pain, and general physicalsymptoms, but then to further combine and analyze sensor acquired datawith additional factors that influence the individual experience ofpain, and other related healthcare issues and disease states. Currently,physicians and caregivers rely upon a patient's own description ofsymptoms such as pain, which is an example of a physical outcome thathas defied objective measurement. Today, uni-dimensional scales are usedto evaluate pain. A commonly used scale is the numerical rating scale(NRS), which typically consists of scores 0-10, with the far leftdenoting “no pain” and the far right end of the scale as “worst painimaginable”. In general, it is difficult for a subject to accuratelydescribe their pain, but especially while under duress, or for examplepatient populations that may struggle with communication, such aschildren, elderly patients suffering from dementia, and those who do notspeak the same language as the treating medical professional. Clinicalfindings that can be seen—a broken bone on an x-ray, for example—do notnecessarily correlate well with the severity of pain the patientperceives. Elderly patients experience pain twice as often as thoseunder the age of 60 which is thought to relate to their inability toaccurately communicate pain and intensity or source of pain (Herr K etal, Assessment and measurement of pain in older adults. Clin GeriatricMed, 2001 August; 17(3):457-vi) (Weiner D et al, 1999. Pain in nursinghome residents: An exploration of prevalence, staff perceptions, andpractical aspects of measurement. Clin of J Pain. 1999; 15:92 [PubMed:10382922]). People afflicted by pain may find the rough tools oflanguage inadequate to convey the character and intensity of theirexperience and its significance to them. This can be a substantialbarrier to obtaining adequate treatment (Werner, A., and K. Malterud.2003. It is hard work behaving as a credible patient: Encounters betweenwomen with chronic pain and their doctors. Social Science & Medicine57(8):1409-1419). According to the Institute of Medicine, (IOM, 2011),pain and its severity, how it evolves, and the effectiveness oftreatment depend on a constellation of biological, psychological, andsocial factors, such as the following:

-   -   Biological—the extent of an illness or injury and whether the        person has other illnesses, is under stress, or has specific        genes or predisposing factors that affect pain tolerance or        thresholds;    -   Psychological-anxiety, fear, guilt, anger, depression, and        thinking the pain represents something worse than it does and        that the person is helpless to manage it (Ochsner, K., J.        Zaki, J. Hanelin, D. Ludlow, K. Knierim, T. Ramachandran, G.        Glover, and S. Mackey. 2008. Your pain or mine? Common and        distinct neural systems supporting the perception of pain in        self and other. Social Cognitive and Affective Neuroscience        3(2): 144-160);    -   Social—the response of significant others to the pain-whether        support, criticism, enabling behavior, or withdrawal—the demands        of the work environment, access to medical care, culture, and        family attitudes and beliefs.        Beyond the lack of a currently available objective measures for        pain and more recent agreement that pain, and other complex        chronic diseases, are a constellation of biological,        psychological, and social factors there is still further need to        address existing issues with under-treatment of patients        suffering from chronic pain resulting from shortened hospital        stays and lack of at-home monitoring and telemedicine. As        outlined in IOM's Relieving Pain in America report: In 2007,        almost half of Emergency Department patients presented with pain        that was severe 22% or moderate 23%. (Niska et al, National        Hospital Ambulatory Medical Care Survey: 2007 emergency        department summary. National Health Statistics Reports 26.        Hyattsville, Md.: National Center for Health Statistics) Chest        or abdominal pain was the leading reason for the visit among        those aged 15-64, while chest or abdominal pain plus shortness        of breath was the leading reason for the visit among those 65        and older. There were 10 million inpatient surgeries and 17.4        million hospital outpatient surgeries in 2009 (AHA (American        Hospital Association). 2011. Trendwatch chartbook 2011. Tables        3.1 and 3.4.        http://www.aha.org/aha/research-and-trends/chartbook/index.html        (accessed Mar. 3, 2011)). Between 10 and 50 percent of people        having regularly performed surgical operations—groin hernia        repair, breast and thoracic surgery, leg amputation, and        coronary artery bypass surgery—go on to experience chronic pain,        often due to damage to nerves in the surgical area during the        procedure (Kehlet, et al, Persistent postsurgical pain: Risk        factors and prevention. Persistent postsurgical pain: Risk        factors and prevention. Lancet. 2006; 367(9522):1618-1625).        Today's shorter hospital stays—down, on average, from 7.2 days        in 1989 to 5.4 days in 2009 (AHA, 2011)—and the trend toward        outpatient surgery may not permit sufficient opportunity to        assess patients' postsurgical pain or establish an appropriate        course of postoperative analgesia (perhaps one that can be        administered at home), shown to be effective in hip and knee        replacement, for example (Schug et al. Chronic pain after        surgery or injury. 2011 Pain Clinical Updates 19. Seattle,        Wash.: International Association for the Study of Pain). There        is currently no way to monitor an out-patient's response to        pharmaceutical treatment and the effectiveness of treatment        related to pain and other related chronic disease states.

Recent improvements in sensor technology, powerful and miniaturizedmicro-controllers, systems on a chip (SOCs), low energy wirelesscommunication, and power management add up to the opportunity for newwearable devices that allow for long-term, at-home, patient monitoringof physiologic measurements via patient worn sensors, cloud computingfor data storage and analysis, and integration with networks and mobiledevices provide communication with healthcare providers and healthcaresystems. What is not measured in these devices of the prior art is ameasurement of the severity of pain that a patient is experiencingeither due to an immediate injury or as a chronic result of disease orother infirmary. Using the pain measurement and diagnostic system (PMD)of the present invention, pain is objectively measured to providecurrently unavailable biophysical information that will assist indiagnosis, the selection and validation of treatments, and may providepatient incentives to continue in performing effective treatments. Bytracking and evaluating biophysical measurements, “pain matrix” activityin the form of a pain modulatory circuit with inputs that arise inmultiple areas including cortical sites, the rostral anterior cingulatecortex (rACC), pregenual cingulate cortex, (pCC), somatosensory cortex 1and 2, the thalamus and hypothalamus, insula, the amygdala,periaqueductal gray region (PAG), and additional descending pathwaystructures, and vagal tone may be correlated to determine stress,cognition, emotion, disease states, and evaluation of threat todetermine pain state, modulation of pain, level of health and healing,and the vulnerability toward illness of a patient (Ossipov et al.Central Modulation of Pain. The Journal of Clinical Investigations:November 2010; 120(11): 3779-3787.)

Pain measurements may also assist physicians in prescribing properdosage based on the patient's reaction to medication. Patients arereceiving inadequate access to pain medications due to thewell-publicized abuse of opioids and the subsequent reluctance of themany in the medical community to write prescriptions fornon-institutionalized patients. According to researchers at the CDC, toreverse the epidemic of opioid drug overdose deaths and preventopioid-related morbidity, efforts to improve safer prescribing ofprescription opioids must be intensified (Paulozzi L J, Jones C, Mack K,Rudd R. Vital signs: overdoses of prescription opioid painrelievers—United States, 1999-2008. MMWR Morb Mortal Wkly Rep 2011;60:1487-92). Between 2013 and 2014, the age-adjusted rate of deathinvolving synthetic opioids, other than methadone (e.g., fentanyl)increased 80% (Rudd et al. Increases in Drug and Opioid OverdoseDeaths—United States, 2000-2014. CDC: Morbidity and Mortality WeeklyReport (MMWR). Jan. 1, 2016/64(50); 1378-82). In 2014, there wereapproximately one and a half times more drug overdose deaths in theUnited States than deaths from motor vehicle crashes (CDC. Wide-rangingonline data for epidemiologic research (WONDER). Atlanta, Ga.: CDC,National Center for Health Statistics; 2015. Available athttp://wonder.cdc.gov). Adequate pain treatment and follow-up may bethwarted by a mix of uncertain diagnosis and societal stigma consciouslyor unconsciously applied to people reporting pain, particularly whenthey do not respond readily to treatment (IOM, 2011).

There is currently no objective measure for pain and as a resultphysicians struggle to both diagnose and treat pain. A pain monitorwould address this major health crisis by facilitating healthcareproviders' prescribing of opioid pain relievers; in particular,prescribing the appropriate dose. American Geriatrics Society citesdelays in access to prescribed opioids for nursing home patients,including those who are terminally ill, and the American Cancer Societyhas recognized the frequent inaccessibility of opioids necessary fortreating some pain (IOM, 2011). According to the White House actionplan, between 2000 and 2009, the number of opioid prescriptionsdispensed by retail pharmacies grew by 48 percent—to 257 million.However, based on increased regulations to limit opioid abuse,twenty-nine percent of primary care physicians and 16 percent of painspecialists report they prescribe opioids less often than they thinkappropriate because of concerns about regulatory repercussions (Breueret al, Pain management by primary care physicians, pain physicians,chiropractors, and acupuncturists: A national survey. Southern MedicalJournal 2010 103(8):738-747).

Accurate medication dosage, early intervention, and physician educationare necessary. The following is a list of potential savings fromimprovements in pain prevention, care, education, and research per IOM2011 Relieving Pain in America report:

-   -   better treatment of acute pain, through education about        self-management and better clinical treatment, in order to avoid        the progression to chronic pain, which is more difficult and        more expensive to treat and generates high health care        utilization;    -   reductions in health problems and complications of other        physical and mental diseases and conditions associated with        chronic pain that also are expensive to treat;    -   more cost-effective care of people with chronic pain when        self-management and multimodal approaches are used more often,        primary care physicians are educated and empowered to treat most        people with pain appropriately, and unnecessary diagnostic tests        and procedures and referrals to specialists are avoided;    -   better tailoring of treatment to individuals based on new        research findings and integration of those findings into        patterns of care. Patient Controlled Analgesia (PCA) devices        which enable the patient to self-administer pain medicine are        used to administer medications in institutional settings. While        there is currently no commercially available way to objectively        measure pain, and rising concern over abuse of opioids and other        prescriptions, PCA's are utilized and do have advantages.        Research shows PCA is superior to intermittent injection of pain        medication, even by the IV route (D'Arcy, Y. (2007). Pain        pointers: Safe pain relief at the push of a button. Nursing Made        Incredibly Easy, 5(5), 9-12). Patients use less narcotic, do not        have to wait for the nurse to bring the medication, and have        greater overall satisfaction with better analgesia and lower        pain scores than patients who request analgesia from the nursing        staff (Smeltzer, S., et al. (2008). Textbook of medical surgical        nursing (11th ed.). Philadelphia: Lippincott). By controlling        pain, patients can move more readily, take deep breaths and        ambulate earlier, reducing the risk of post-operative        complications (D'Arcy, Y. (2008). Keep your patient safe during        PCA. Nursing, 38(1), 50-55).

Despite these advantages there are negatives. For example, they cannotbe readily used, if at all, for infants, toddlers, and other who cannotoperate the device due to either a physical disability such as a spinalcord injury or individuals unable or unwilling to understandinstructions for use. Patients who are obese or asthmatic, or thosetaking drugs that potentiate opiates, such as sedatives or hypnotics,muscle relaxants and antiemetics, should not use PCA. Patients withsleep apnea should not use PCA (D'Arcy, Y. (2011). New thinking aboutpostoperative pain management. OR Nurse, 51(11): 28-36). Also, currentPCA devices continue to operate based upon the subjective measure ofself-assessment. Without a means to normalize patient self-assessmentinconsistent treatment remains an issue for patients. PCA combined withan objective measure for pain using the PainTrace medical devices andcomponents and features of the pain measurement and diagnostic system(PMD) of the present invention may alleviate many existing issues.

SUMMARY OF THE INVENTION

The pain measurement and diagnostic system (PMD) of the presentinvention uses medical devices to acquire data, and physiologicalmeasurements, related to pain and demographics, medical information,activities, and patient and healthcare provider information furtheracquired through PMD specific components and features to establishbaselines for both healthy patients and for patients that may besuffering from various disease states. Using the PMD, collected datarelated to pain and associated physiological measurements, aretransformed to diagnostic indicators, or healthcare provider tools,based on factors related to patient demographics, comorbidities,interventions, and other known contributors that affect the overallexperience of pain, and additionally are indicators of health, includinggenetics, biomarkers, past experiences, pain matrix neurologicalmodulation of pain, activities, and emotional and cultural influences.The PMD will acquire and store pain measurements, physiologicalmeasurement, and relevant data, correlating with surveys and the current“gold standard”, Visual Analog Scale (VAS) and similar scales for theself-report of pain to translate collected data to establish a moreaccurate and reliable scale of pain measurement, and related diseasediagnosis and monitoring, based on physiological measurements and thebiopsychosocial factors related to the experience of pain.

Recent findings through neurological research have determined theexistence of a brain-based “pain matrix” responsible for the processingand modulation of pain. The central nucleus of the amygdala (CeA) iscentral to this pain matrix with neurological connections linked to theperiaqueductal gray region (PAG), responsible for descending painpathways from the brain, and cortical sites that together with theamygdala provide emotional-affective modulation of cognitive functionsin pain (Ossipov). et al. Central Modulation of Pain. The Journal ofClinical Investigations: November 2010; 120(11): 3779-3787, Neugebaueret al. Forebrain pain mechanisms. Brain Res Rev. 2009; 60 (1): 226-242).In particular, the amygdala produces the largest asymmetry, and researchhas shown that the amygdala is a critical component of the pain matrix.(Veinante P et al. The Amygdala between sensation and affect: a role inPain. J Molec Psych 2013, 1:9http://www.jmolecularpsychiatry.com/content/1/1/9). Studies haveevidenced that only the right central nucleus of the amygdala (CeA) hasbeen related to both acute and chronic pain. (Ossimov, 33-40), (Ji, G.et al. Hemispheric lateralization of pain processing by amygdal neurons.JNeurophysiol. 2009; 102 (4): 253-2264, Carrsquillo, Y. et al.Hemispheric lateralization of a molecular signal for pain modulation inthe amygdala. Mol Pain. 2008; 4:24). By measuring EDA using thecontralateral placement of sensors, or electrodes, direct measurementsof brain pain processing from the “pain matrix” demonstrate the“collection of brain regions that are involved in neurologicalfunctions, including cognition, emotion, motivation, and sensation aswell as pain” (Ossipov), et al. Central Modulation of Pain. The Journalof Clinical Investigations: November 2010; 120(11): 3779-3787). Largeasymmetric differences in EDA between the left and right side have beendemonstrated upon direct stimulation of particular brain regions, someof which form the aforementioned “pain matrix.” Boucesin in,Electrodermal Activity page 41, summarizes three main pathwaysconnecting the central nervous system (CNS) to EDA. In particular, thepathway termed “EDA1” arises from the limbic region which includes theamygdala as a brain region that elicits ipsilateral EDA (Mangina C A, etal. Direct Electrical Stimulation of Specific Human Brain Structures andBilateral Electrodermal Activity. Int J Psychophysiol, 1996 22(1-2),1-8; Mangina C A, et al. Even-related Brain Potentials, BilateralElectrodermal Activity and Mangina-Test Performance in LearningDisabled/ADHD Pre-adolescents with Severe Behavioral Disorders asCompared to Age-matched Normal Controls. Int J Psychophysiol, 200037(1), 71-85; Boucsein W. Electrodermal Activity. (2nd Ed.); Page 41.Springer-Verlag (New York 2012).

The use of contralateral sensors for the measurement of EDA and acorrelation of these measurements to pain is described in U.S. Pat. No.6,347,238 to Levengood and Gedye, and others. However, these findingswere presented somewhat in isolated experiments and the devices usedpresented challenges in sensitivity and repeatability. In Burke, U.S.Pat. No. 8,560,046, a device that reliably measured pain was disclosed,however the integration of collected data with other biophysicalmeasurements and particularly with ipsilateral measurements was notdescribed.

This patent outlines an integrated pain measurement and diagnostic thatbuilds and improves on previously granted claims for contralateralsensor placement in the measurement of autonomic nervous system functionand pain matrix activity. The PMD combines a series of data managementsystems to acquire biosignals, integrate patient information, performdiagnosis, and treatment interventions and deliver pain measurement anddiagnostic outcomes that provide useful and useable information for theHCP. In addition to the diagnosis of pain, the pain measurement devicesof the PMD also provide early diagnosis of intestinal distress,allergies and respiratory infection, sports injury related to tendon andligament damage, as well as diagnosis of chronic pain related to backinjury, dental and migraine cases among others. Using the PMD it hasdemonstrated statistically significant correlation to patientself-report of pain and the evaluation of pre- and post-treatment painstates as well as the aforementioned disease states.

The PMD as described herein evaluates physiologic measurements, trackspatient activity, interacts with patient via questions pertinent totheir diagnosis, and aids decisions around on-going treatment regimensand alterations to improve outcomes. The physiologic measurementsevaluated by the PMD may include, but are not limited to, pain-relatedasymmetric biosignals specific to the present invention, heart rate,heart rate variability, photoplethysmogram (PPG), blood pressure, skintemperature, movement, GSR, and other vital signs. Through the analysisand continual integration of data, the PMD has an evolutionary nature,in that it will constantly be evaluating data input from a number ofdifferent sources, for example health care providers who are gatheringbiometrics data on patients that may be suffering from various diseasestates, new research and journal references related to specific diseasestates, and biophysical data through multiple biosensors used inmonitoring the patient with the initial scope of analysis directed toinclude evaluations of acute and chronic pain as it relates tointerventions. Through the gathering of data points that comprisebiological, psychological, social measures, and other relevant datafields combined with the disease state diagnostic data points, the PMDwill store, data mine, integrate, and transform the gathered data in aHIPAA compliant manner, or in an appropriate fashion to protect patientprivacy rights, in order to parallel and integrate data on patientsusing a biopsychosocial platform, or one that comprises otherappropriate factors for data points, to further increase theunderstanding of a disease state or evaluate an intervention. The PMDmay further correlate device generated measurements of pain and thecentral nervous system activity as related to respiratory sinusarrhythmia, heart rate and heart variability, respiration,photoplethysmogram (PPG), movement, and skin temperature measurementsfrom other sensors in order to determine pain matrix activity and vagaltone that may provide information on the vulnerability of the patient tostress and illness. (Loggia et al, Autonomic responses to heat pain:Heart rate, skin conductance, and their relation to verbal ratings andstimulus intensity. Pain. 2011; 152 (3): 592-598). By measuring themanifestation of pain in the nervous system combined with data regardingbiological, behavioral, environmental, psychological, and socialfactors, the PMD may further derive statistical computations of patientand population factors and isolate factors to be used for diagnosis toincrease the understanding of various disease states via themulti-dimensional transformation of data through the analysis using thepain and physiological measurements generated by the device, andcomponents and features integrated within the PMD platform.

The individual nature of a patient's interpretation of pain and thecurrent biospsychosocial approaches to treatment of complex diseasestates presents barriers to fully understand a patient's experience andhow pain relates to treatment and successful outcomes. The PMD, as anintegrated device, network, and software system, removes subjectiveanalysis and resolves issues of patient inconsistencies and limitationsby integrating objective sensor measurements of pain and “pain matrix”central nervous system activity with health information, demographics,and physiological measurements through a unique graphical user interface(GUI) that makes data accessible and useful for health care providers(HCP) and patients. The PMD uses pain measurement acquisition softwareto normalize and correlate measurements from for example the pain matrixand associated signals, and integrates aspects of this measured paindata to other collected sensor data to more effectively present thebiophysical state of a patient at specific time points. The PMD furtherintegrates information from specific fields through specific questionsrelated to patient activities and disease states. For example, amigraine patient may receive a series of questions as designated timepoints related to pain inflections that represent a change in painstate. The collected responses are correlated and may show an increasein pain that is related to activities such as eating, exercise, stress,and other daily interactions that may identify the source of pain orexasperation, or improvement, of the diseased or healthy state. The PMDfurther integrates patient health status, physical biosignal devicemeasurements, diagnosis, research, and healthcare provider (HCP)intervention and management in order to reinforce positive patientemotions, to educate, to promote healthy activities, and to encouragecompliance to improve outcomes through remote patient engagement. ThePMD further provides a personal health record storage platform that willadditionally function as universal health record allowing individualhealth and activity data and electronic health record data to becombined for analysis. The analysis of health information, demographics,and physiological measurements with pain matrix and nervous systemmeasurements presented through the PMD System of the present inventionwill result in integration of data and ongoing monitoring that benefitsthe healthcare community and individuals with custom and global analysisof health factors, specific disease and health related data, andeffective treatment options to ultimately improve understanding of adisease state, or general health, related influencing factors, and bestpractices for safe and effective treatment interventions and regimens.The integration and optimization of this data within contextualtimeframes and associated patient knowledgebase presented by theBioTraceIT analysis application software of the PMD can dramatically aidan HCP in diagnosis, patient monitoring, patient engagement, treatmentoptions, and acceptable dose limits.

It is an objective and advantage of the present invention to integratedevice generated pain measurements and other biometric sensors andbiopsychosocial data collected within a graphical user interface fortracking and evaluation of a patient's health status and response totreatment as the subjective nature of pain has many components that canbe potentially objectified when combined with a physiologicalmeasurement of pain as acquired by the PainTrace device 14 andintegrated within the PMD 10; pain measurement and diagnostic system(Chapman et al, Pain and Stress in a Systems Perspective: ReciprocalNeural, Endocrine, and Immune Interactions. J Pain. 2008 February;9(2):122-145).

It is a further object and advantage of the present invention that thePMD utilizes a computer processing system having memory and data storageto process the electrical activity of a pain matrix and central nervoussystem measurement device.

It is a further object and advantage of the present invention that thePMD utilizes a computer processing system having memory and data storageto process the electrical activity of a pain matrix and central nervoussystem measurement device by measuring the differential of voltage orcurrent between at least two matching electrodes and normalizing anelectric signal to determine a value level representative of objectivequantitative measure of pain matrix activity and displaying and storingdata from the pain measurement device and using the collected data inthe evaluation of health and wellness.

It is a further object and advantage of the present invention that thePMD utilizes a computer processing system having memory and data storageto process the electrical activity of a pain matrix and central nervoussystem measurement device by measuring the differential of voltage orcurrent between at least two matching electrodes contralaterally placedand by measuring the voltage or current differential between andnormalizing an electric signal to determine a value level representativeof an objective measure of pain matrix activity and displaying andstoring data from the pain measurement device and using the collecteddata in the evaluation of health and wellness.

It is a further object and advantage of the present invention that thePMD utilizes a computer processing system having memory and data storageto process the electrical activity of a pain matrix and central nervoussystem measurement device by measuring the differential of voltage orcurrent between at least two matching electrodes ipsilaterally placedand by measuring the voltage or current differential between andnormalizing an electric signal to determine a value level representativeof an objective measure of pain measuring and displaying and storingdata from the pain measurement device and using the collected data inthe evaluation of health and wellness.

It is a further object and advantage of the present invention that thePMD utilizes a computer processing system having memory and data storageto process the electrical activity of a pain matrix and central nervoussystem measurement device by measuring the differential of voltage orcurrent between at least two matching electrodes contralaterally placedwith the voltage or current differential between at least two matchingelectrodes ipsilaterally placed to calibrate measurements of the painmatrix and central nervous system activity and displaying and storingdata from the pain measurement device and using the collected data forthe evaluation of health and wellness.

It is a further object and advantage of the present invention that thePMD utilizes a computer processing system having memory and data storageto process the electrical activity of a pain matrix and central nervoussystem measurement device by measuring the differential of voltage orcurrent between at least two matching electrodes contralaterally placedwith the voltage or current differential between at least two matchingelectrodes ipsilaterally placed to determine and validate a value levelrepresentative of an objective measure of pain matrix and centralnervous system activity and displaying and storing data from the painmeasurement device and using the collected data for the evaluation ofhealth and wellness.

It is a further object and advantage of the present invention that thepain matrix and central nervous system measurement device of the PMDwill be worn over longer periods of time as a “wearable” at-home monitorfor pain and health monitoring with data collected using components andfeatures of the PMD.

It is a further object and advantage of the present invention that thePMD provide alerts based on data collected from the pain matrix andcentral nervous system measurement device that deviates from set levelsbe transmitted to associated healthcare providers.

It is a further object and advantage of the present invention that thePMD provides for the administration of medication through an automatedpump dispenser based on data collected from the pain matrix and centralnervous system measurement device.

It is a further object and advantage of the present invention that thePMD provides for the activation through a security code of a dispenserfor medication based on data collected from the pain matrix and centralnervous system measurement device.

It is a further object and advantage of the present invention that datacollected from one or more physiological monitors of the PMD formeasuring multiple physiological signs of a subject such as pain, heartrate, heart rate variability, skin temperature, electrodermal activity(EDA), photoplethysmogram (PPG) readings, skin conductivity, motion,tension and compression is used for the evaluation of health andwellness of a patient.

It is a further object and advantage that the PMD of the presentinvention collect data from one or more physiological monitors formeasuring multiple physiological signs.

It is a further objective and advantage that the PMD includes componentsand features to interact with the patient based on their diagnosis andmonitored changes in pain levels.

The present invention is related to a bioanalytical analysis systemusing pain measurements to diagnosis and measure the effectiveness oftreatment outcomes, the system comprising a device for measuring painmatrix activity; a plurality of BioTrace Factors related to biophysical,biological, psychological, social, environmental, and demographicinformation; and wherein deflections in measurements of pain matrixactivity are combined with BioTrace Factors to determine theeffectiveness of a patient's treatment. The combination of pain matrixactivity and BioTrace Factors provides a quantitative measure of pain.The quantitative measure of pain matrix activity correlates withself-reporting of pain using a numerical rating scale. The bioanalyticalanalysis system comprises 10-60 messaging triggered by a combination ofpain matrix activity, BioTrace Factors, and integrated journaling. Theplurality of BioTrace Factors of the bioanalytical analysis systemcomprising contribution factors and factor impact levels. Thecombination of pain matrix activity measurements and BioTrace Factorsprovide a PainTrace Factor reflective of an individual patient'sexperience to pain. The combination of BioTrace Factors and a PainTraceFactor provide BioTrace Progress Score reflective of the effectivenessof a patient's treatment and measurement of a patient's compliance tothat treatment.

In some embodiments measurements of pain matrix activity of thebioanalytical analysis system are made without applying a voltage, byapplying a range of voltages or currents. The device for measuring painmatrix activity of the bioanalytical analysis system has sensors and insome embodiments a float current is applied to the sensorsintermittently. The sensors of the device for measuring pain matrixactivity may be placed contralaterally, ipsilaterally, in pairs placedcontralaterally and in pairs placed ipsilaterally, and in someembodiments two pairs of ipsilateral sensors are placed contralaterally.The device for measuring pain matrix activity of the bioanalyticalanalysis system has a load resistor having resistance of between 0.5 kohms and 900 k ohms. The load resistor may be a variable resistor and acalibration method may incrementally increase resistance by applyingvoltage to generate a linear resistance curve. The variable resistor maybe adjusted using the linear resistance curve to produce maximum currentflow.

The bioanalytical analysis system using pain measurements to diagnosisand measure the effectiveness of treatment outcomes may comprise anoxious stimulus caliper that applies a consistent and repeatable amountof pressure for a consistent period of time. By acquiring pain matrixactivity measurements from the applied stimulus using the noxiousstimulus caliper a baseline of pain tolerance may be generated. Thebioanalytical analysis system may comprise one or all of the followingcomponents a motion detector, a heart rate monitor, a heart ratevariability monitor, a blood pressure monitor, a galvanic skin responsemeasurement device, and a skin temperature measurement device. In someembodiments, the device for measuring pain matrix activity of thebioanalytical analysis system comprising a pain matrix monitoringdevice, heart rate monitor, heart rate variability monitor, bloodpressure monitor, galvanic skin response measurement device, temperaturemeasurement device, and motion detector. The bioanalytical analysissystem may comprise SaaS, PaaS and on demand computing services and ashared resource database through a web browser or other interface. Thebioanalytical analysis system may comprise an electronic circuit for theinitialization, identification, location, acquisition, control andcommunication to the device for measuring pain matrix activity.

The present invention is related to an autonomic function monitoringdevice, comprising: a pain matrix activity measurement device havingsensors, a data acquisition system; and wherein deflections inmeasurements of pain matrix activity are used to determine the levels ofa patient's pain and health. The pain matrix activity measurement of theautonomic function monitoring device provides a quantitative measure ofpain. The quantitative measure of pain matrix activity correlates withself-reporting of pain using a numerical rating scale. The measurementsof pain matrix activity may be made without applying a voltage or byapplying a range of voltages and currents. In some embodiments, a floatcurrent is applied to the sensors intermittently. The sensors of theautonomic function monitoring device may be placed contralaterally,ipsilaterally, in pairs placed contralaterally and in pairs placedipsilaterally, and in some embodiments two pairs of ipsilateral sensorsmay be placed contralaterally.

The autonomic function monitoring device wherein the device formeasuring pain matrix activity having a load resistor having resistanceof between 0.5 k ohms and 900 k ohms. In some embodiments, the loadresistor is a variable resistor and resistance is incrementallyincreased and voltage is applied to generate a linear resistance curve.In applying calibration methods, the variable resistor may be adjustedusing the linear resistance curve to produce maximum current flow. Theautonomic function monitoring device may comprise a noxious stimuluscaliper that applies a consistent and repeatable amount of pressure fora consistent period of time. The pain matrix activity measurements fromthe applied stimulus using the noxious stimulus caliper may be used togenerate a baseline of pain tolerance. In some embodiments, theautonomic function monitoring device may comprise one or all of a motiondetector, a heart rate monitor, a heart rate variability monitor, ablood pressure monitor, a galvanic skin response measurement device, anda skin temperature measurement device. The autonomic function monitoringdevice comprising SaaS, PaaS and on demand computing services and ashared resource database through a web browser or other interface. Theautonomic function monitoring device comprising an electronic circuitfor the initialization, identification, location, acquisition, controland communication to a plurality of sensors.

The present invention is related to an activity monitor to measure pain,that in some embodiments may comprise contralateral sensors measuringpain matrix activity without applying voltage. In other embodiments,activity monitor to measure pain may comprise ipsilateral sensors byapplying voltage. The activity monitor to measure pain comprising one orall of a heart rate monitor, a heart rate variability monitor, a motiondetector, a blood pressure monitor, a galvanic skin response measurementdevice, and a skin temperature measurement device. The activity monitorto measure pain may comprise a sensor track. The activity monitor tomeasure pain may comprise a sensor cluster. The activity monitor tomeasure pain may comprise an electronic circuit for the initialization,identification, location, acquisition, control and communication to aplurality of sensors.

The present invention is further related to a sensor track, comprising aflexible sensor attachment device having a track and conductive strip;and wherein the flexible sensor attachment device provides for theattachment and electrical connection to a plurality of electrodes andsensors. The sensor track may comprise a Velcro strip for the attachmentof the sensor track to clothing. The sensor track may comprise anadhesive strip for the attachment of the sensor track to skin, clothingor other surfaces. The sensor track may comprise an electronic circuitfor the initialization, identification, location, acquisition, controland communication to a plurality of sensors. The sensor track maycomprise wireless communication circuitry. The sensor track may comprisecommunication connectors to add separate sensor tracks and additionalelectrodes and sensors to the sensor track.

The present invention is related to a method of quantitatively measuringpain, comprising establishing a baseline by measuring the pain matrixactivity during noxious stimulus; monitoring pain matrix activity anddeflections from the established baseline; establishing BioTrace Factorsbased on patient biophysical data, patient and population demographicsand self-reported measurements of pain; establishing a PainTrace Factorbased on the integration of data from pain matrix activity measurementsand BioTrace Factors; monitoring patient pain matrix activity throughtreatment; and identifying pre-treatment and post-treatment deltasindicative of the change in pain state; and correlating the measureddeltas with associated pain scales.

The present invention is a method of measuring the effectiveness oftreatment outcomes using measurements of pain matrix activity,comprising monitoring pain matrix activity and deflections to establisha quantitative measure of pain; monitoring and collecting LifeTraceITdata based on patient activity, engagement, compliance and integratedjournaling; applying an iterative analysis to BioTrace Factors,PainTrace Factors, LifeTraceIT data, related to a patient andintegrating this analysis to generate an individualized BioTraceProgress Score which will be determined on an ongoing basis thatcontinues monitoring of patient actions, physiological data, treatmentinterventions, and pain matrix activity; which will further be combinedwith associated trends, population clusters, current research andhistorical medical records in assessing the effectiveness of treatmentoutcomes.

Other objects and advantages of the present invention will becomeobvious to the reader and it is intended that these objects andadvantages are within the scope of the present invention. To theaccomplishment of the above and related objects, this invention may beembodied in the form illustrated in the accompanying drawings, attentionbeing called to the fact, however, that the drawings are illustrativeonly, and that changes may be made in the specific constructionillustrated and described within the scope of this application.

BRIEF DESCRIPTION OF THE DRAWINGS

Several embodiments of the present invention will now be described byway of example only, with reference to the accompanying drawings inwhich:

FIG. 1 is a diagrammatic representation of an embodiment of a painmeasurement and diagnostic system (PMD) network that may be in aclinical or hospital setting in an implementation of the presentinvention;

FIG. 2 is a diagrammatic representation of an embodiment of a serversystem and integration of one or more server systems, computers, mobiledevices, biophysical devices and sensors and pain measurement deviceswithin the PMD network in an implementation of the present invention;

FIG. 3 is a diagrammatic representation of an embodiment of applicationcomponents in an embodiment of the PMD of the present invention;

FIG. 4 is a diagrammatic representation of an embodiment of thePainTrace application component in an embodiment of the PMD of thepresent invention;

FIG. 5 is a diagrammatic representation of an embodiment of thePainTrace application component in an embodiment of the PMD of thepresent invention;

FIG. 6A is a diagrammatic representation of an embodiment of the painmeasurement sensors (referred to herein as the PainTrace sensors orPainTrace device sensors) that provide data to an embodiment of thePainTrace application component in an embodiment of the PMD of thepresent invention;

FIG. 6B is a diagrammatic representation of an embodiment of a PainTracedevice that provides data to an embodiment of the PainTrace applicationcomponent in an embodiment of the PMD of the present invention;

FIG. 6C is a diagrammatic representation of another embodiment of thePainTrace sensors that provide data to an embodiment of the PainTraceapplication component in an embodiment of the PMD of the presentinvention;

FIG. 6D is a diagrammatic representation of a further embodiment of thePainTrace sensors that provide data to an embodiment of the PainTraceapplication component in an embodiment of the PMD of the presentinvention;

FIG. 6E is a diagrammatic representation of a still further embodimentof PainTrace sensors and PainTrace measurement devices with sensors thatprovide data to an embodiment of the PainTrace application component inan embodiment of the PMD of the present invention;

FIG. 6F is an exploded view of a diagrammatic representation of theembodiment of the PainTrace sensor and holder of FIG. 6C that providedata to an embodiment of the PainTrace application component in anembodiment of the PMD of the present invention;

FIG. 6G is a diagrammatic representation of a still further embodimentof a PainTrace measurement device with sensors that provides data to anembodiment of the PainTrace application component in an embodiment ofthe PMD of the present invention;

FIG. 6H is a diagrammatic representation of the still further embodimentof a PainTrace measurement device with sensors of FIG. 6G that providesdata to an embodiment of the PainTrace application component in anembodiment of the PMD of the present invention;

FIG. 6I is a diagrammatic representation of a still further embodimentof a PainTrace measurement device with sensor integrated with a bloodpressure monitor to provide data to an embodiment of the PainTraceapplication component in an embodiment of the PMD of the presentinvention;

FIG. 6J is a diagrammatic representation of a still further embodimentof a PainTrace sensor device that may be used with the PainTracemeasurement device and blood pressure monitor of FIG. 6I to provide datato an embodiment of the PainTrace application component in an embodimentof the PMD of the present invention;

FIG. 7A is a front view of a diagrammatic representation of anembodiment of the PainTrace device with sensor installed on a wristbandto provide data to an embodiment of the PainTrace application componentin an embodiment of the PMD of the present invention;

FIG. 7B is a rear view of a diagrammatic representation of an embodimentof the PainTrace device with sensor installed on a wristband to providedata to an embodiment of the PainTrace application component in anembodiment of the PMD of the present invention;

FIG. 7C is a front view of a diagrammatic representation of anotherembodiment of only the PainTrace sensor installed on a wristband toprovide data to an embodiment of the PainTrace application component inan embodiment of the PMD of the present invention;

FIG. 8A is a side view of a diagrammatic representation of an embodimentof the PainTrace device with sensors to provide data to an embodiment ofthe PainTrace application component in an embodiment of the PMD of thepresent invention;

FIG. 8B is a rear view of a diagrammatic representation of an embodimentof the PainTrace device with sensor installed on a wristband to providedata to an embodiment of the PainTrace application component in anembodiment of the PMD of the present invention;

FIG. 9A is an internal side view of a diagrammatic representation of anembodiment of the PainTrace device with sensor to provide data to anembodiment of the PainTrace application component in an embodiment ofthe PMD of the present invention;

FIG. 9B is a rear view of a diagrammatic representation of an embodimentof the PainTrace device of FIG. 9A to provide data to an embodiment ofthe PainTrace application component in an embodiment of the PMD of thepresent invention;

FIG. 9C is a rear view of a diagrammatic representation of an embodimentof the PainTrace sensor of FIG. 9A to provide data to an embodiment ofthe PainTrace application component in an embodiment of the PMD of thepresent invention;

FIG. 10A is a perspective view of a diagrammatic representation of anembodiment of the PainTrace sensor to provide data to an embodiment ofthe PainTrace application component in an embodiment of the PMD of thepresent invention;

FIG. 10B is a perspective view of a diagrammatic representation of anembodiment of the PainTrace sensor connector;

FIG. 10C is a perspective view of a diagrammatic representation of anembodiment of the PainTrace device connector;

FIG. 11A is a perspective view of a diagrammatic representation of anembodiment of the PainTrace sensor, sensor connector, and deviceconnector in an unlocked position;

FIG. 11B is a perspective view of a diagrammatic representation of anembodiment of the PainTrace sensor, sensor connector, and deviceconnector in a locked position;

FIG. 12A is a front view of a diagrammatic representation of anembodiment of the PainTrace sensor, sensor connector, and deviceconnector in an unlocked position;

FIG. 12B is a front view of a diagrammatic representation of anembodiment of the PainTrace sensor, sensor connector, and deviceconnector in a locked position;

FIG. 13 is a block diagram of an embodiment of components of PMDcircuitry in an embodiment of the PMD of the present invention;

FIG. 14 is a diagrammatic representation of an embodiment of thePainTrace application component in an embodiment of the PMD of thepresent invention;

FIG. 15A is a diagrammatic representation of an embodiment of a PMDsensor track and sensors to provide data to an embodiment of thePainTrace application component in an embodiment of the PMD of thepresent invention;

FIG. 15B is a diagrammatic representation of an embodiment of theconnection of two PMD sensor track and sensors to provide data to anembodiment of the PainTrace application component in an embodiment ofthe PMD of the present invention;

FIG. 15C is an end view of an embodiment of the PMD sensor track and anembodiment of a sensor to provide data to an embodiment of the PainTraceapplication component in an embodiment of the PMD of the presentinvention;

FIG. 15D is an end view of a further embodiment of the PMD sensor trackand an embodiment of a sensor to provide data to an embodiment of thePainTrace application component in an embodiment of the PMD of thepresent invention;

FIG. 16 is a diagrammatic representation of an embodiment of theBioTraceIT application component incorporating data from the LifeTraceITapplication component in an embodiment the PMD of the present invention;

FIG. 17 is an embodiment of the PainTrace data and BioTrace Factors usedto determine a PainTrace Factor and pain tolerance threshold in anembodiment the PMD of the present invention;

FIG. 18 is a flow chart showing an embodiment of BioTrace Factors thatmay be used to develop the BioTraceIT analysis in an embodiment the PMDof the present invention;

FIG. 19 is a diagrammatic representation of an embodiment of theBioTraceIT application component in an embodiment the PMD of the presentinvention;

FIG. 20 is a diagrammatic representation of another embodiment of theBioTraceIT application component in an embodiment the PMD of the presentinvention;

FIG. 21 is a diagrammatic representation of still another embodiment ofthe BioTraceIT application component in an embodiment the PMD of thepresent invention;

FIG. 22 is a diagrammatic representation of an embodiment of theMediTraceIT application component in an embodiment the PMD of thepresent invention;

FIG. 23 is example PainTrace data showing pain measurements before andafter treatment in an embodiment of the PMD of the present invention;

FIG. 24 is example PainTrace data as compared to VAS self-reporting inan embodiment of the PMD of the present invention;

FIG. 25 is example PainTrace data collected over a sixth month period ofa horse suffering from laminitis in an embodiment of the PMD of thepresent invention; and

FIG. 26 is example PainTrace data showing the changes in painmeasurements before and after treatment for twenty patients in anembodiment of the PMD of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is a pain matrix and central nervous systemmeasurement and diagnostic system (PMD) 10 that includes one or moremedical devices for the objective measurement of pain matrix activityand a method of data collection and analysis of pain measurements todiagnose disease states and health status and validate patienttreatments and outcomes. The PMD 10 may be implemented on local networkand other devices having compatible electronics. The computer systemsand electronic devices are integrated within networks and servers tocommunicate with one or more pain matrix and central nervous systemmeasurement devices, biosensors, computer systems, devices andcommunication systems. In a first embodiment as shown in FIG. 1, the PMD10 may be implemented within a local area network 12 for example may bewithin a clinical or hospital environment or utilizing electronicdevices capable of communicating with cloud computing services forpersonal or remote monitoring. The PMD 10 may be implemented through oneor more devices such as a smartphone to collect and transmit patientdata to a cloud network, hospital network, medical offices, assistedliving, or other point of care or place for acquiring, viewing, andanalyzing biophysical data, or for telemedicine each referred to hereinas an “acquisition environment” 1 and to an external BioTraceIT PMDserver system 18 to be accessible to compile, review and store patientdata and biometric information. The PMD 10 may provide various levels ofaccess to medical devices and specific components and features that maybe implemented through one or more software applications. Administrativelevels may be set and managed within administrative tools of thesoftware application. Software application variants and access levelsprovide for medical devices, features and components to be specific toparticular facets of treatment and to the patient and medicalprofessionals treating the patient. For example, within the acquisitionenvironment 1, the PMD 10 may provide features and components accessibleby the patient for personal patient monitoring of biophysical factorsand activities. Additional, features and components may be provided forhealth care providers (HCPs) for point of care monitoring and additionalfeatures for physicians and others for remote telemedicine monitoringwith levels or security and patient anonymity provided as requiredwithin the different levels of access. Within the “acquisitionenvironment” 1, the devices and sensors collecting patient data may haveinternal communication systems to display and transmit data within thePMD 10 that may be accessible through an intranet and/or internetconnection for viewing and monitoring collected patient data on a mobiledevice such as a smartphone, smartwatch iPhone, iPad, iPod, smartwatch,wearable, augmented reality glasses, or tablet computer 22 for thepatient to access the data themselves and/or for an HCP, physician,physical therapist or other attendants of the patient, or payers,administration, or independent researchers to access the data.

The PMD 10 may be implemented through a secure server and be accessiblethrough a web browser user interface for hospital HCP staff to registerand collect data from the sensors and data collection devices within ahospital network 16. Within a hospital network firewalls 36, redundancyand other security protocols to protect patient data are available withnetworking hubs 30, servers 32, and communication devices 34 toestablish communications to the acquisition environment 1 and todistribute data through a communication network 20 to the HCPs andothers requiring the patient data. The communication network 20 mayinclude the access to the patient data through the PMD 10 on tabletcomputers 22, nursing station dashboards 24, smartphones 28, and throughother devices within the communications network 20.

Access to the patient data through the PMD 10 may further be providedthrough devices directly wired and connected to the pain matrix andcentral nervous system measurement or other biosensors for datacollection such as through a USB port for acquisition environments 1that may be remote for internet access. For example, in a battlefieldmedical unit that requires patient data and analysis without havingaccess to external resources. The patient data may further be stored onthe device such as on memory and data storage devices on a PainTracedevice 14 to be transmitted when wired or wireless access becomesavailable. The PMD 10 may further be pre-loaded to be the onlyaccessible application and monitoring system on a digital device forpatient, HCP, or physician use in environments without internet access,such as for an elderly patient within their home in a remote location.Data from the PMD 10 using the digital devices may be linked throughanalog phone lines or cellular communications 26 to providecommunication to HCPs and others in the form of alerts, voicemail, text,and/or email. Abbreviated data and information may also be accessiblethrough the PMD 10 via software applications or specific components andfeatures of one or more software applications accessible on a smartphonethrough cellular communications 26. Therefore, accessibility to thepatient data through the PMD 10 is provided in a number of forms toaccommodate various acquisition environments 1 where the patient may beinfirmed within a hospital, be within a care or rehabilitation facility,be within their own home, and/or be in remote locations with minimal orno access to the internet. In this way, the PMD 10 may provide thecollected data that may be from the one or more pain matrix and centralnervous system measurement devices 14 and biosensors 11 in an accessibleand comprehensive manner to provide useable and interpretableinformation to the patient, HCPs and physician at each of the differentaccessible levels of PMD's software application and hardware dataacquisition components and features.

The sensors and devices integrated with the components and features ofthe PMD 10 may importantly be in the form of the pain matrix and centralnervous system measurement sensors and devices referred to herein asPainTrace devices 14. The PainTrace devices 14 may collect and displaydata within the device 14 and transmit data within the acquisitionenvironment 1 and within the hospital network 16 and other networkspreferably using Bluetooth, Wi-Fi, Near Field Communication (NFC) and/orother communication protocols such as through wireless modems wheresensor data is collected and recorded from patients within theacquisition environment 1.

The collected data may further be transmitted through a secure internetconnection to the BioTraceIT PMD server system 18 that also hasfirewalls 38, redundancy and security protocols to protect data. Thedata may preferably be transmitted either directly from a pain matrixand central nervous system measurement device or other sensors or from aclinical or hospital network without identifying information such as thename or address of the patient. However, information about the patientthat may include biological, psychological, social, and environmentalfactors may be included and all data including patient identifyinginformation may be immediately accessible to assist with treatmentwithin the acquisition environment 1 at the point of care. In thismanner all data may be accessible within the hospital network 16 andde-identified information can be correlated and stored within a databaseand may be accessible through the BioTraceIT PMD server system 18 as rawor processed data from sensors including the PainTrace device 14 withcollection times and dates to be used with the biological,psychological, social, and environmental factors where data of all typesmay be available for data mining, correlation and pattern analysis toidentify and develop BioTrace factors as described herein. TheBioTraceIT PMD server system 18 also has a server 40, network hubs 42and computer systems 44. The BioTraceIT PMD server 18 may also hostfirmware images for updates to the software components and features ofthe PMD 10. Through some applications of the PMD system 10 as describedherein, data may only be accessible through a direct wire connectionsuch as using a USB connection to the pain matrix and central nervoussystem measurement device or through a near field communication (NFC) inorder to provide limited access and secure an autonomous device such asa drug dispenser or devices within remote acquisition environmentwithout internet access.

As shown in FIG. 2, the PMD system 10 may be implemented in computerhardware and computerized equipment. For example, components andfeatures of the PMD system 10 can be performed using one or more painmatrix and central nervous system measurement devices 14 and/or otherbiosensor medical device systems 11 to measure biophysical readings suchas heart rate, heart rate variability, photoplethysmogram (PPG), bloodpressure, skin temperature, movement, GSR, and other vital signs. ThePMD 10 may further be implemented through other digital communicationsdevices and/or one or more personal computers and data servers. Forexample, components and features of the PMD 10 and BioTraceIT serversystem 18 may be implemented on a computer system 3 which is shown forthe purpose of illustrating an embodiment of hardware components thatmay be used for implementation of the PMD 10. The present invention isnot limited to the computer system 3, software or hardware componentsshown, but may be used with any electronic data processing system suchas found in personal or other digital communications devices, cellularphones and other mobile or wearable devices, tablet computers, or anyother systems for the acquisition, processing, transformation, displayand distribution of analog and digital data. The computer system 3includes a server computer 4 having a microprocessor-based unit 5 (alsoreferred to herein as a processor) for receiving and processing softwareprograms and for performing other processing functions. An output device7 such as a visual display is electrically connected to the processorunit 5 for displaying user-related information associated with thesoftware, e.g., by means of a graphical user interface. A keyboard 8 mayalso be connected to the processor unit 5 for permitting a user to inputinformation to a software program. In addition to using the keyboard 8for input, a mouse 6 may be used for moving a selector on the display 7and graphical user interface, or alternatively a touch screen of asmartphone, smartwatch iPhone, iPad, iPod, wearable, augmented realityglasses, or tablet computer, or any other input device may be providedfor choosing an item and providing input to the processor 5. The painmeasurement devices which in some embodiments may be referred to hereinas the PainTrace devices 14 and other biophysical devices and sensors 11are integrated with components and features of the PMD 10 which may bein the form of software and/or hardware. These feature and components ofthe PMD 10 as described herein may initialize communication toelectrodes and sensors and setup communication protocols to one or morePainTrace devices 14 and other biophysical devices and sensors 11 toprovide instructions in the form of starting, stopping, setting andadjusting the time, sampling rates, and other parameters of dataacquisition. The PMD 10 may also associate the PainTrace devices 14 andother biophysical devices and sensors 11 with a patient, treatmentprotocol, one or more HCPs and/or physicians, a clinical or hospitalnetwork, and other associative information related to the patient,treatment, and acquired data as described herein. Within the PMD 10,PainTrace devices 14 and other biophysical devices and sensors 11 may beautomatically located and identified through these associations toassist an HCP and clearly present acquired data as being from a specificpatient in accordance with appropriate healthcare guidelines. Thecomponents and features of the PMD 10 may also set alerts and alarmswith specific contact information to directly contact the HCP orphysician in the case of an emergency, access a PainTrace device 14 andother biophysical devices and sensors 11 to replace or reset values, andprovide tracking of the frequency of pain matrix and central nervoussystem measurements or other sensor readings. Various components andfeatures of the PMD 10 are accessible from the pain measurement device14, from other biophysical sensors 11, from a tablet computer orsmartphone used by the HCP or physician, and/or through the network orserver system as described herein. For example, a HCP who is on call mayreceive an alert and could adjust the frequency of readings to acquiremore data from the pain measurement device via their smartphone underacceptable conditions and security within the acquisition environment 1and network 16. It is to be appreciated that the input is not limited tothe known input apparatus and methods but includes input methods anddevices which may yet be developed.

Memory and data storage, in any form, can be included and is illustratedas a hard-disk device such as computer readable storage medium 2, whichcan include software programs, and is connected to the microprocessorbased unit 5 for providing a means of inputting the software programsand other information to the microprocessor based unit 5. Multiple typesof memory can also be provided and data can be written to any suitabletype of memory. Memory can be external and accessible using a wired orwireless connection, either directly or via a local or large areanetwork, such as the Internet. Still further, the processor unit 5 maybe programmed, as is well known in the art, for storing the softwareprogram internally. The output device 7 provides visually to the usertransactional, interactive or variable data that has been subject totransformations. The output device 7 can be a monitor, touch screen orother visual computer or digital device screen or graphical userinterface (GUI), a chart recorder, a printer or other output device thatprovides a visual or other representation of a final output from theprocessor unit 5. The output device 7 can also be an output device inthe form of a data collection device such as a pain matrix and centralnervous system measurement device or other biosensor medical devicesystem that provides the transactional data as an analog or digitaloutput and/or as a digital file. The processor unit 5 provides means forprocessing and transforming the transactional, interactive or variabledata to produce readily discernible, informational and organized imagesand data on the intended output device or media. Those skilled in theart will recognize that the present invention is not limited to justthese mentioned data processing and data transformation functions.

The server computer 4 can store a computer program product having aprogram stored in the computer readable storage medium 2, which mayinclude, for example: magnetic storage media such as a magnetic disk ormagnetic tape; optical storage media such as an optical disc, opticaltape, or machine readable bar code; solid state electronic storagedevices such as random access memory (RAM), read only memory (ROM) orflash memory data storage devices. The associated computer program anddata server may be implemented through application software 17 on a SaaS(Software as a Service), PaaS (Platform as a Service) or on demandcomputing service such as a Cloud or shared resource database through aweb browser or other interface. Secure logins with passwords may beprovided to remotely access the different levels of software 17 throughan intranet or internet connection 13. One or more of the devices toaccess the PMD system 10 may be connected wirelessly, such as by acellular link, Wi-Fi wireless, Bluetooth technology or other technologywhere the device is either directly connected or via a network. It is tobe appreciated that such devices can be mobile devices using voicecommands to enter and access data using digital devices that may be inthe form of a camera, PDA, iPod, iPhone, iPad, tablet computer,augmented reality glasses, digital display, smartphone, or cell phone,smartwatch, wearable, and other digital devices that can be used as aprocessing unit, data transformation unit, a display unit, or a unit togive processing instructions, and as a service offered via the internet.

The PMD 10 implemented within the BioTraceIT PMD server system 18 may inan embodiment have security protocols 9, one or more databases 19, anadministrative tool module 21, data acquisition module 23 to accept andtransform data from a pain matrix and central nervous system measurementdevice or other sensor data, a communications module 25 to collect andtransmit data which may be in the form of emails, text messaging, voicemessaging and other communication protocols, a data analysis module 27,and data compilation module 29. The BioTraceIT PMD server system 18 mayacquire, compile and store data from multiple pain matrix and centralnervous system measurement devices and other sensors within variousacquisition environments 1 such as one or more networks that may includea hospital network 16 and in-home monitoring of patients. The BioTraceITPMD server system 18 further provides for the transmission, collectionand storage of reference data 31 through an intranet or internetconnection as shown in FIG. 2. The PMD 10 through the communicationmodule 25 may further provide software and firmware updates andreference updates to maintain the most currently available informationfor HCPs and other users of the PMD 10.

The PMD 10 may be implemented as a mobile application for an iPhone,iPad, iPod, smartphone, smartwatch, wearable, augmented reality glasses,tablet computer, and/or other mobile digital device. The PMD 10 mayfurther be developed on a computer operating system to be implementedwithin the system servers 32 of the hospital network 16 for example as anursing station dashboard application 24, running on a Windows-basedcomputer system. In any format, the PMD 10 provides for the Health CareProviders (HCP) to select a pain matrix and central nervous systemmeasurement device such as the PainTrace device 14 or other sensor ormedical device 11, and correlate the sensor data with patientinformation, as well as monitor the collected data, and receivethreshold-based alerts. In one embodiment, the PMD 10 may communicatesolely within the hospital server system 16 in order to optimize refreshtimes for data storage and for receiving updates from the centralizedserver source 16. The collected data may then be compressed andtransmitted to the external BioTraceIT PMD server system 18 at repeatedintervals, to reduce required bandwidth and transmission time. Infurther embodiments, the PMD 10 including one or more pain matrix andcentral nervous system measurement devices 14 or other biosensors 11 maybe implemented on a mobile device for patients to monitor individualhealth readings.

As shown in FIG. 3, the diagram represents the different components andfeatures of software applications and hardware in the form of dataacquisition devices of the PMD some or all of which may be included invarious forms of the PMD 10 that may be used by patients, healthcareproviders, insurance providers, hospital administration, and others. Thecomponents and type of data contained within each component as describedherein is provided with a general context and application of the data.The data acquisition module 23 of the PMD 10 is essentially a corePhysiological Readings component 52 to collect data from pain matrix andcentral nervous system measurement devices such as the PainTrace device14 and to collect other sensor data used for analysis within the PMD 10.This data is collected and combined with a “Patient” health datacomponent 54 and demographics of patient populations referred to as a“Disease Specifics” component 56 including research, factors affectingpain perception, acute and chronic disease states and references.Components and features within the PMD 10 may further provide a“Treatment” component 58 presenting protocols and outcomes of prescribedtreatments. In an embodiment, the PMD 10 combines the physiologicalreadings, in this instance related to measurement of the pain matrix andcentral nervous system, with pertinent data related to but not limitedto the research and data analysis components, to produce “objective painreadings” and evaluate pain matrix and central nervous systemmeasurement readings with respect to patient biophysical factors,diagnoses, specific data field input, and treatments.

The Physiological Readings component 52 acquires data that includes themeasured pain matrix and central nervous system data acquired byPainTrace device 14 and other sensor oriented readings related to thebody's reaction to stress, disease, and health-related experience. ThePatient data component 54 provides data in the form of biologic datarelated to specifics about patient age, health, and medical history thatmay include but not be limited to biological, psychological, social, andenvironmental factors. This data may be provided or supplemented by thepatient as part of their integration to treatment and additionally bepulled from electronic health records, notes, and other data acquiredregarding a patient. Patient data when transferred to the BioTraceIT PMDserver system 18 may be de-identified per appropriate healthcareguidelines. Using the data analysis module 27, collected data, such asdata collected from the PainTrace device 14 and other biosensors 11, maybe normalized, averaged, and correlated to specific activities, foods,exercise and other biophysical actions of the patient. Components andfeatures of the PMD 10 utilize and combine the transformed collecteddata with physiological measures, and biological, psychological, social,and environmental factors to develop bioclustering matrices, andbipartite graphs that using weighting algorithms are correlated andranked to develop what are referred to herein as BioTrace Factors 150.By transforming and correlating raw data, which is innately subjective,objective physiological measures are generated and data from thePainTrace device 14 and pain matrix and central nervous systemmeasurement and diagnostic technique becomes increasingly meaningful andmay be used to evaluate a patient's perception and tolerance of pain toimprove proper diagnosis and treatment.

To further standardize physiological response to pain and subsequentpain matrix and central nervous system measurement using the PainTracedevice 14 within the PMD 10, an adjunct device that delivers astandardized noxious stimulus is integrated into the PMD 10 and thediagnostic technique. The introduction of painful, or noxious, stimulusbased on current central stimuli tests such as the supraorbital pressureor sternal rub, or peripheral tests such as squeezing the lunula area ofthe finger or toe nail, or squeezing the side of the finger will berepeatable and measurable through the use of calibers and compressionand tension gauges to apply stimulus with consistent and repeatableamount of pressure to standardize the applied stimulus. Stimulus will beapplied over a standardized time while measuring patient pain levels, orpain matrix activity, pre-, intra-, and post-stimulus. “Standard stimuliresponse” may be measured during periods of health, such as an annualvisit, or during injury or illness to establish baseline “pain matrixresponse levels”. Patient pain matrix activity will then be applied tostandardized scales to be used with other factors to create a PainTraceFactor which references this baseline pain matrix activity. The painmatrix response levels are further cross-referenced to other knownfactors that influence a patient's tolerance to pain which include butare not limited to age, sex, race, blood pressure, previous injury, painsurveys, and with additional physiological and psychosocial thatindividualize measurements which may be some of the components that arereferred to herein as BioTrace Factors 150. The contribution of thesefactors with the patient's baseline pain matrix activity measured usingnoxious stimuli are used to derive the patient's personal PainTraceFactor.

The pain matrix and central nervous system measurement data and BioTraceFactors 150 may further be implemented within the Treatment component 58of the PMD 10 to track and measure the objective physiological measuresas related to treatment protocols and outcomes. Connecting treatmentsand comparing physiological readings related to treatments may result inbetter understanding of how effective each treatment is and additionallysince it is also related to patient data provided within the Patientcomponent 54 there is the opportunity to specialize and individualizetreatment options for the individual patient. Furthermore, analyzing andconnecting treatment, patient demographics, and acute and chronicdisease states may not only produce improvements in individualized carebut also provide a broader knowledge of disease states resulting in moreeffective care for all patients and associated costs savings.

A broader knowledge of the efficacy of treatments from the collection ofphysiological readings during treatment and the integration and analysisof this data as it relates to reference materials 31 is provided usingthe Disease Specifics component 56. This component of the PMD 10 mayintegrate knowledge on specific acute and chronic ailments and diseaseswith information related to the BioTrace Factors 150 of a specificpatient to provide for more meaningful understanding of physiologicalreadings in multi-factorial disease states, such as the perception ofpain. In addition, this data curated from biomedical, healthcare,clinical, and physiological research can be referenced by appropriateend-users, such as healthcare practitioners, to both educate and makeresources available to medical personnel. The derived Biotrace Factordemographics may be grouped in major categories (bio, psycho, social,environmental, behavioral, etc.) deemed relevant based on patient data.The development and ranking of the BioTrace Factors 150 may continuallyand iteratively be updated through the integration of information ondisease states and treatments in reference materials 31 and can becross-referenced using the data compilation module 29 of the PMD 10generating trends and potential improvements in care. Clinical trialdata can additionally be linked using the components and features of thePMD 10 to create a greater connection between research, outcomes, andpotential new treatments.

Using the Physiological Readings component 52 with the Patient component54, the Disease Specific component 56, and Treatment component 58information will not only generate normalized, correlative, objectivemeasures of primarily subjective symptoms but furthermore may beconnected with patient self-reported, and sensor monitored, lifestyleimpacts software applications referred to herein as the LifeTraceITcomponent 60 of the PMD 10; healthcare practitioner software andapplications referred to as the BioTraceIT component 62 of the PMD 10 toassist in decision making for testing, diagnosis and treatment; and thefinancial impact of treatment through spend and efficacy trackingreferred to herein as the MediTraceIT 64 of the PMD 10 to create acomprehensive system for integrating the many factors that impact asubjective physiological experience of patients. Transformed data may beutilized to create patient specific electronic communications such asthrough text messaging, via dedicated or other mobile devices, to engagethe patient to potentially evaluate sources of pain matrix inflections,and generate patient engagement to educate, encourage healthy habits andbehaviors, and track activity as it relates to device generated physicaldata. Changes in pain levels may trigger a series of questions. Thisfeature of the LifeTraceIT software 60 would represent “integratedjournaling” which uses physiological questions based on biosignal dateto request specific information from the affected individual to aid insource detection of pain or unhealthy stimulus. The LifeTraceIT 60software application as a component of the PMD 10 uses transformed datacombined with defined patient interaction platforms to engage patients.

The healthcare BioTraceIT component 62 of the PMD 10 generates normativeand BioTrace Factors data for the healthcare practitioner and willpromote improved understanding of a patient's experience, and anincreased ability to evaluate treatment efficacy. The BioTraceITcomponent 62 within the PMD 10 may benefit a patient during emergentcare where the measure of pain matrix and central nervous system data orPainTrace data may indicate the degree and the location of pain throughan analysis of data using components and features of the PMD 10 duringexamination protocols. The BioTraceIT component 62 may further benefitphysicians, nurses, physical therapists and others by providing patientmetrics to give insight into the patient profile, contributing factors,comorbidities, and then associate relevance of these factors as itrelates to the patient's experience and provide associated treatmentalgorithms and clinical data for consideration by the HCP.

The LifeTraceIT component 60 of the PMD 10 may optionally also beprovided and accessible on the PainTrace device 14 and/or other medicaldevices at a patient level of access and/or through a mobile digitaldevice software app. A patient may first provide health informationthrough certain surveys and data forms for healthcare and healthinstitutions utilizing the PMD 10 and/or PainTrace sensor 14 and othermedical sensors and devices. During the process of completing andentering healthcare survey data or specific fields a patient may also beoffered the opportunity to utilize the LifeTraceIT component as personalhealth record software. The LifeTraceIT component 60 of the PMD 10 maybe provided in several interface modes to the subscriber such as thefollowing:

-   -   Personal Lifestyle Tracking Component—The LifeTraceIT component        60 may be used to log activities, physiologic measures,        treatment, prescription drug use, and other patient related        data. The LifeTraceIT component 60 may collect data acquired        using the PainTrace device 14 and other physiological        measurement sensors, and collect data related to time spent in        exercise, sleep, nutrition, and other activities and to collect        emotional data to help a patient track and use their own        LifeTraceIT data to develop and improve treatments.    -   Healthcare Network Component—the personal data collected from        the patient noted above may additionally be connected with        preferred healthcare providers, hospital systems, and networks        including the BioTraceIT PMD server system 18. Ultimately, the        patient is improving their opportunity to regain health and        understand their physiological symptoms by sharing their        personal data with healthcare providers. By utilizing this data        within the BioTraceIT software component 62 data analysis may        lead to the ability for an HCP to better evaluate the efficacy        of treatment options, lifestyle options, and personal choices to        improve both personal, and global health and disease related        outcomes. This data may further be used by the healthcare        community to improve understanding of treatment, lifestyle, and        demographic factors to create optimized healthcare interventions        with specialized focus.    -   Guidance and Messaging Component—Additionally, the LifeTraceIT        component 60 may also provide suggestions and information to        help the patient during treatment. The LifeTraceIT component 60        of the PMD 10 may gather data from other health tracking        software applications a user may choose to use and with the        appropriate licensing, that data will be incorporated into        LifeTraceIT and BioTraceIT. The data may be integrated with        other information and collected data within the PMD 10 to help        the patient adapt and change routine and behavior patterns        within and as required by the prescribed treatment. The        LifeTraceIT component 60 may also provide for customized        messaging to be created and used as messaging patterns by a        doctor, HCP or other provider to provide to a patient to        motivate, answer questions and relieve anxiety as behavioral        patterns of the patient change. For example, to improve outcomes        of chronic pain patients a“interaction algorithm based on device        acquired physiological data may generate a messaging pattern to        help the patient improve decision making around the use of pain        prescriptions and triggers to influence coping mechanisms to        address pain non-pharmacologically. Physicians may choose to        initiate treatment oriented messaging patterns to make        accessible to the patient over a prescribed period of time, such        as through a daily message or at specific times such as when        administering medication. A pain inflection may trigger the        “10-60 pattern” which utilizes 10 questions about the last 60        minutes to determine source, motivation, or intervention related        data. The messaging may also include changes in BioTrace Factors        150 as described herein that have resulted as an example in        decreased pain in order to motivate and show the value of the        collected data and of maintaining the requirements of the        prescribed treatment. Alternatively, pain or other biophysical        measurements by the PMD 10 may trigger alerts that prompt        messaging or questions for the patient such as when pain        thresholds are elevated due to for example a migraine. The        LifeTraceIT software, or a device associated with the PMD 10,        would initiate “10-60 Messaging” to engage the patient to        determine the source of the pain at the time of pain inflection.        Because migraines may be triggered by food, clothing dyes,        perfumes and other chemicals, a text message is sent from the        PMD 10 asking questions about the environment, activity or what        food was recently consumed, for example 10 questions to receive        information about the last 60 minutes. The response would be        collected and evaluated to assist in determining what may be        causing the elevation in pain. For example, the patient answers        that they had a meal recently and they select from a list of        foods that they ate or enter an alternative food entry if not        included on the list. They are asked: the location; what kind of        seating—i.e. a chair with a back or a stool without a back are        options; were they indoors or outdoors; if outdoor were they        near vegetation and what type; was there a beverage—if so was it        alcohol, soda etc. The list is defined by disease state or        injury to determine a source of the pain inflection detected by        the Pain Measurement device 14 within the specific period of        time when an elevated pain measurement is measured. The        responses from the 10-60 questions are integrated into the PMD        10 and then combined with the LifeTraceIT software application        to transform a physiological symptom into a diagnostic and        tracking tool. Other “10-60 Messaging” scenarios may include        patient engagement, education, and compliance among others.        Any prescribed medical test and/or treatment is associated with        costs, to patient, the hospital, and to insurance providers with        current methodologies within the healthcare system resulting in        disconnects through complicated coding and coding subsets that        must be entered for each step of treatment. Integration of the        PMD 10 with electronic health records can eliminate duplicated        work and augment the use of codes. For large hospitals, a        completely different set of personnel from the HCP may enter the        treatment codes that generate bills to patients and insurance        companies. While financial considerations should not limit or        restrict treatments offered to patients, additional knowledge on        duration and efficacy of treatments and the related costs can        more quickly lead to the modification of ineffective treatments.        The MediTraceIT component 64 of the PMD 10 integrates health        records and tracks the treatment and medications prescribed for        each patient. This information is clearly presented to        physicians, HCPs and others with a timescale minimizing workload        and reducing duplication and errors. Within the MediTraceIT        component features to adding coding and annotation to treatment        are provided so that billing specific to the treatment received        may be tabulated. The PMD 10 further provides within the        effective and clear summary of the combination of treatments        prescribed to a patient their relative effectiveness and cost to        assist an HCP with identifying best treatment options, optimize        costs, and furthermore help to identify abuse of medication by a        patient. The PMD 10 provides the MediTraceIT component 64 as a        spend and efficacy tracking system that combines healthcare        analysis from the BioTraceIT component 62 with physiological        measurements from collected data from sensors and related        lifestyle information from the LifeTraceIT component 60. By        tracking healthcare outcomes, treatment options, effectiveness,        and costs the MediTraceIT component 64 of the PMD 10 allows        health networks, hospitals, providers, and payors to analyze        best treatment options. Additionally, with the LifeTraceIT        component 60 insurance premium refunds could be realized by        rewarding compliant patients for following evidence-based        protocols with documented outcomes. Using the “MediTraceIT        Treatment Protocols”, meaning those with statistical correlation        between treatment and outcome, a patient's compliance via        self-report compared to treatment regimen and outcomes can be        calculated for significance (meaning the patient actually did        what they are instructed to do resulting in an effective        outcome) and subsequently the patient would receive a refund of        a stipulated portion of their insurance premium. The MediTraceIT        component 64 of the PMD 10 may therefore provide a method to        motivate patient compliance and subsequently drive down        healthcare costs by improving outcomes.

In an embodiment of the present invention as shown in FIG. 4, a dataacquisition module 23 of the PMD 10 is the PainTrace application 70interface for the presentation and analysis of data acquired from thePainTrace device 14 and biophysical devices and sensors 11. ThePainTrace device 14 as a component of the PMD system 10 provides themeasurement and integration of sensor data which may be in the form ofbiosignals, to analyze pain matrix activity. The PainTrace application70 includes remote and embedded PMD circuitry that provides the controlof the acquisition, communication and management of one or morePainTrace devices and/or biophysical devices and sensors 11. ThePainTrace application 70 further includes location and proximityfeatures to automatically locate, initialize, track and associatedelectrodes, the PainTrace device 14, and other medical devices 11 with aspecific patient, HCP, physician, clinical or hospital network. ThePainTrace application allows an HCP to view the PainTrace readings ofthe pain matrix and central nervous system and parasympathetic nervoussystem's activity as it relates to pain, health, and treatment with asdesired other collected biophysical data. Data from the PainTrace sensor14 and/or biophysical devices and sensors 11 may be collectedcontinually, using the data acquisition module 23 of the PainTraceapplication 70 within the PMD 10 for display on the device and/or onother digital devices through a network 12 within a clinical or hospitalenvironment and/or the BioTraceIT PMD server system 18. The dataacquisition module 23 may improve data quality by reducing noise andanomalies, and the data may be sampled and compressed for display withinthe PainTrace application 70. The PainTrace data signal 72 may bepresented in relationship to an axis 74 denoting a zero baseline wherethe PainTrace device may measure the difference in either voltage orcurrent from EDA measurements taken from sensors placed contralateral,and at times ipsilateral, on the patient with multiple biosignal sourcespotentially contributing to the overall measurement based on timedmonitoring and integration. Data signals 72 that are equal to or veryclose to the zero baseline indicate a balance in EDA from each side ofthe body and correlate to balanced pain matrix activity which does notrepresent a pain state. Data signals 72 either above or below the zerobaseline indicate a difference in contralateral EDA and an increase inpain matrix activity. Therefore, for the patient with signal peaksextended further, in the direction denoting pain whether that ispositive or negative as determined by the scaling system, from the axis74 an increase in pain is indicated. As shown in FIG. 4 a patient with anegative reading, below the baseline, represents a degree of pain. Apatient with an initial negative reading will represent an increase inpain via an increasingly more negative number, or a negative deflectionaway with respect to the zero baseline 74. The delta between the initialpain measurement and subsequent pain measurement represents the increaseor decrease in pain. Therefore, in this example a deflection in thepositive direction denotes a relative decrease in pain or less pain. ThePMD 10 transforms this deviation acquired as a raw biosignal into a painscore more analogous to the currently used standard scales forself-report that equate no pain as equivalent to zero and equate theworst pain as equivalent to 100. Using the PMD 10, scales of pain can bestandardized based on a patient's BioTrace Factors 150 and derivedPainTrace Factor 102. For example, young patients may consistently havemore positive numbers and therefore a negative reading would be moresignificant in this patient population. Conversely, elderly patients mayhave generally more negative, or less positive, readings and therefore anegative number is associated with a different level of pain. The PMD 10uses information about the patient and other patients of similardemographics in normalizing the pain matrix activity data collected togenerate BioTrace Factors 150 and derive a PainTrace Factor 102 specificfor the patient but normalized to a scale based on similarly situatedpopulations. Additional readings from ipsilateral sensors may also betaken and used to calibrate and validate pain readings where this datais also used by the PMD 10 to normalize collected pain matrix activitydata, as described herein.

A tolerance level 76 may be calculated specifically for the patientbased on BioTrace Factors 150 and acquired PainTrace data as describedherein. The tolerance level 76 may denote levels of intolerable pain forthe patient and may be determined from maximum values of pain previouslyrecorded for the patient, with the threshold increasing if the currentmaximum value is exceeded. The collected data may therefore benormalized based on patient factors, individual response to pain, anddemographics that have a known influence on pain and the tolerance level76 may be presented above or below the zero baseline 74 as dictated bythe BioTrace Factors of the patient. The PainTrace data signal 72 may bepresented with a time block 78 to associate the onset and duration ofpain to physiological activities during the acquisition of data from thePainTrace device 14. The HCP may customize a time scale 73 to view dataas longer or shorter periods of time from minutes, to hours, to days andother time periods as desired. The PainTrace data may further becombined and presented with information on patient activity, theadministration of medication and other information within the time scale73. The time block 78 may include scroll features 80 to adjust the timescale 73 for review of data.

The PainTrace application 70 further provides icons for data entry anddrop-down fields where applicable with a first icon providing for theadministration of medication to be entered by a patient or HCP. The Medicon 84 may expand and present a list of medications currentlyprescribed for the patient, and/or provide a data entry window for apatient or HCP to enter information about for example an over thecounter pain reliever. The Med icon 84 may also be integrated withelectronic medical records (EMR) to decrease duplication or to augmentEMR when desired. The type of administration icons 85 for the medicationmay provide a quick reference and verification for the HCP of when andwhat type of medication the patient was administered over a period oftime. The Med Administration icon 85 allows a patient or HCP to drag anddrop a Medication Note 88 along the timeline or integrate related datafrom electronic medical records. If the administration of medication isover a period of time such as through intravenous administration (IV)the HCP may drag and expand the indicator 98 over the time period ofadministration or for any desired period of time. A Nutrition icon 90may provide for the patient or HCP to enter information on food intake,a Sleep icon 92 may provide time of sleep, an Activity icon 94 mayprovide other activities, such as work, alcohol consumption, or othersocial activities, and an Exercise icon 96 may provide time exercisingwith any icon selected providing an indicator 98 that may be expandedalong the timeline to show the actual time spent. In an embodiment, thePainTrace application 70 may provide for data entry, however inpreferred embodiments that data may be captured from the LifeTraceITcomponent 60 of the PMD 10 that provides patient physiological andactivity data, from the MediTraceIT component 64 of the PMD 10 thatwould integrate, as an adjunct to electronic health records, all of thepatients prescribed medication, treatment protocols, interventions,other information from patients health records, and costs into thePainTrace application 70, and/or the BioTraceIT component 62 of the PMD10 that may add a prescribed treatment protocol within the timeline fora patient to follow and adhere to. The patient may then confirmcompletion of steps within the treatment protocol. The PainTraceapplication 70 within the PMD 10 provides a basic, focused pain readingof the patient and groups and displays this information within specifictimeframes, treatments and activities of the patient to make the painmeasurement data and biophysical information useful for a patient orHCP. A BioTrace Progress Score 280 evaluating all these factors can begenerated for each patient as a quick reference to cumulatively trackpatient progress and improvement or decline in outcome. Physicians canfurther evaluate cumulative progress by viewing individual data setsincluding BioTrace Factors 150 that influence the cumulative BioTraceProgress Score 280.

The PainTrace application 70 may further provide Average PainMeasurement Readings (PMR) 100 over any selected period of time and thePainTrace Factor 102 based on a scale derived from the measuredphysiological data and the BioTrace Factors of the patient. Theindividual pain matrix response can be measured in relation to acontrolled and standardized noxious stimulus. As described above,central nervous system test such as the supraorbital pressure or sternalrub, or peripheral tests such as squeezing the lunula area of the fingeror toe nail are repeatable and measurable through the use of calibersand compression and tension gauges to standardize the applied stimulusin comparison to current test procedures which deliver pressure orstimulus in a non-standard fashion based on a physician's or healthcareprovider's manual touch. The individual pain matrix response levels arerecorded in response to the stimulus as a baseline during generalphysical exams to establish baseline scores at time of injury orillness. The standard noxious stimulus combined with BioTrace Factors150 form a portion of the data that is transformed into a patient'sPainTrace Factor 102. A Contribution Factor 104 as described hereinpresents the level that an individual biological, behavioral,environmental, psychological, and social factors, the BioTrace Factors150 relate to the PainTrace Factor 102. The PainTrace application 70 ofthe PMD 10 may also provide additional physiological measurements suchas heart rate variability 302 which may be used to determine a patient'svagal tone to provide indicators for HCP on the patient's reaction tostress, disease states, and the vulnerability toward illness. (Guntheret al. Critical Care 2013, 17:R51 http://ccforum.com/content/17/2/R51).In instances where the PainTrace Factor 102 is reflecting hyperactivepain matrix activity but the heart rate variability 302 is demonstratingmisaligned, or hypoactivity, in relation to the PainTrace Factor 102this may serve as a tool for a physician to identify a source ofunexplained chronic pain. Vagal tone and vagus nerve activity has beenlinked to pain relief via endogenous release of endorphins. A flaghighlighting a disparity in these two diagnostic indicators may serve asa tool for further testing and attention to a potential medical issue.Napadow, V et al. Evoked Pain Analgesia in Chronic Pelvic Pain Patientsusing Respiratory-gated Auricular Vagal Afferent Nerve Stimulation. PainMed. 2012 June; 13(6): 777-789. Published online 2012 May 8. doi:10.1111/j.1526-4637.2012.01385.x). Within any PMD 10 component a patienticon 106 provides access to patient data that may be displayed throughthe LifeTraceIT component 60 or other patient data applications. Otherfunctional features 108 of the PMD may be provided to save, print oremail data, and create reports, from within the PMD display.

The PMD 10 may provide a slider 110 to view and compare data over arange of days or even weeks to find outliers and anomalies. The datasignal 72 from similar time periods may be selected by expanding theslider 110 over the days of interest. Any number of indicators 98 may beselected for viewing to provide a comparison of these indicators. Inthis example, an administration of medication shows a decrease in thePainTrace data signal 72 shortly after the patient is administered themedication as shown by Medication Note 88 in FIG. 4. However, in FIG. 5,as indicated by Medication Note 88 the medication is administered butthe PainTrace data signal 116 demonstrates an increase in paindelineated by a decline to a more negative number as opposed to theexpected increase to a positive number which would reflect less painafter the administration of pain medications. As indicated by MedicationNote 118, the patient appears to have administered pain medication whenpain levels were well below the axis 74 with little change in thePainTrace data signal 120 which therefore may indicate a tolerance tomedication requiring a change in dosage and/or a possibility of abuse ofthe medication by the patient. The PMD 10 highlighted these disparitieswhich triggered further investigation. Upon review of patient trackedactivity, the increase in pain after Medication Note 88 was attributedto a physical therapy session just prior to the medication administeredin Medication Note 88. Activity information also disclosed that thepatient ate lunch just prior to Medication Note 118. Food would notexplain why medication was taken when the patient was not experiencingpain so the patient was interviewed. Upon questioning it was determinedthat the patient thought that taking medication with a full stomachwould mitigate potential nausea. Understanding the combination of all ofthese variables would not have been possible, or noticed so simply,without the PMD 10. The data, tracking, and physiological signalscombined from PainTrace data signals 72 and the LifeTraceIT application60 are transformed via the PMD 10 to create healthcare tools thatsupport educated decision making and improved healthcare outcomes. Thepatient was further educated about the usage and timing of medication todecrease the incidence of mismanaged acute pain becoming chronic pain,which is much more difficult and costly to treat.

The PainTrace device 14 is capable of measuring the moment-to-momentrelative dominance of the pain matrix and central nervous system throughthe detection of voltage or current differences between a firstPainTrace sensor placed at a location on the left side of the body and asecond PainTrace sensor placed at a similar location on the right sideof the body. Changes in the pain matrix and central nervous systemactivity and vagal tone generate voltages or current that as measuredusing the low offset potential of the PainTrace sensors provide aconsistent quantifiable measurement of pain. The PainTrace sensors arepassive and therefore do not require administering voltage to thepatient. The PainTrace sensors may be of AgCl coated silver substrate,graphene, or other materials as a coating to sufficiently conduct thevoltage changes of the pain matrix and central nervous system activityof a patient as measured across the body mid-line. The PainTrace sensorsmay be wet or dry sensors based on the amount of time the sensors areworn while data is collected. For wet sensors an adhesive may be used toadhere the sensor to the skin and a conductive gel may be pre-applied tothe skin location or to the sensors so that the conductivity isconsistent from the surface of the PainTrace sensor to the skin. Drysensors however may be used for longer periods of wear to monitorchanges in pain over time.

To determine differences in conductivity between the PainTrace sensorson each of the left and right side of the body particularly using drysensors where gel is not pre-applied, measurement of impedance,conductance, and/or other measurements may be made by applying a voltageto the sensors and measuring the impedance for example. Thesemeasurements may also be taken from one of either the left or rightsensors by connecting the sensor to an ipsilateral sensor to takemeasurements from one side of the body. Additional measurements may betaken from ipsilateral sensor pairs or sets on contralateral sides ofthe body and the readings may be used to calibrate the readings for eachof the PainTrace sensors based on differences in skin contact, skinquality, movement, and the other effects of the sensor to skin interfaceand physiologic measurement. Large differences in these measured valuesmay indicate a faulty sensor or limited contact of the sensor surface tothe skin. For example, for smaller differences in impedance withinspecified tolerance levels, the PainTrace application 70 of the PMD 10may apply calibration algorithms to adjust the offset of voltage orcurrent measurements between the left and right PainTrace sensors. Othercalibration methods accessible using the PMD circuitry of the PainTraceapplication 70 may include an iterative linear resistance calibration todetermine a calibration curve as resistance is systematically increasedand/or decreased and voltage or current measurements are taken at eachimpedance adjustment. From the calibration curve a variable loadresistor across the connection of the contralateral and/or ipsilateralsensors is adjusted to optimize voltage and current flow and improve thesignal to noise and quality of the measured signal from the PainTrace orother biophysical sensors. For example, the variable load resistor maybe adjusted to produce maximum current flow. Some embodiments of the PMDcircuitry of the PainTrace application 70 include components to apply afloat current to the electrochemical capacitor of the PainTrace sensorto improve the energy and power characteristics. Losses in efficiencydue to self-discharge during storing or in mishandling of sensors duringapplication may occur, diminishing the overall sensitivity of thesensors. Using the linear resistance calibration or other calibrationmethods a suitable current value may be determined and applied to eachPainTrace sensor during initialization or periodically during andbetween data acquisition to keep the electrochemical capacitor of thePainTrace sensor fully charged.

Additionally, because patient movement may affect the overall quality ofreadings possibly by creating noise spikes or other anomalies, thePainTrace application 70 may use one or more accelerometers on thePainTrace device or on other digital devices or from other sensors tocorrelate noise spikes or anomalies with movement and use thisinformation to smooth, reduce or remove these features from thecollected PainTrace data signal 72. These adjustments provide for thePainTrace application 70 component of the PMD 10 to display and transmitaccurate comparisons of the voltage measurements from the left and rightPainTrace sensors to provide consistent quantifiable measurements ofpain matrix and central nervous system activity via measurement of thecircuit connecting contralateral PainTrace sensors.

As shown in FIG. 6A, the PainTrace sensors 35 in a first embodiment, maybe in the form of two self-adhesive sensors placed in the palm of eachhand, the hypothenar or thenar eminence, of a patient that directlyconnect using wires 33 to the PainTrace device 14 shown in FIG. 6B andas described in U.S. Pat. No. 8,560,045 to Burke. The PainTrace sensors35 may in some embodiments have a holder 39 with a weak adhesive thatholds the sensor 35 in place and that connects the wires 33 to thePainTrace device 14. The PainTrace sensor 35 may be removed from theholder 39 and be disposed of after one or more readings over a definedperiod of time. For example, in a medical physical a pain measurementmay be taken after having the patient sit quietly for a short period oftime of maybe 10 minutes. A measurement is then taken from the patientusing the PainTrace device 14 and the data collected may be used tocalculate a PainTrace Factor 102 that is recorded to be used as abaseline for future pain measurements, even if the patient is notcurrently experiencing any pain. For example, during a general physicalexam, baselines are determined via the PMD with the combination ofstandardized noxious stimuli implemented through controlled and timedpressure. Monitored response to stimuli formulate a patient's painmatrix response levels which in combination with the patients BioTraceFactors 150 develops an individual PainTrace Factor 102 for the patient.The pain matrix response levels are available for immediate use and arestored for subsequent illness or injury requiring pain measurement andphysical diagnosis. The self-adhesive left and right sensors 35 areremoved from the holder 39 and thrown away after the single use. Theholder 39 may in some embodiments, may be compressed to the skin to forma seal thereby creating suction to adhere the sensor in place removingthe requirement for gels. Because removing and replacing each sensorwithin the holder 39 may cause changes in conductance of the surface 37of the PainTrace sensor 35 to the patient's skin additional conductivegel may be applied to the region or sensor if wet sensors are used andthe PainTrace application 70 may measure impedance and/or runcalibration algorithms to adjust voltage measurements from the left andright sensors to be within acceptable tolerance ranges of one another asnecessary based on these measurements.

In a further embodiment of the present invention, as showndiagrammatically in FIG. 6C, a replaceable sensor clip 41 removes therequirement that only the PainTrace sensor 43 be removed forreplacement. The sensor holder 45 is of a rigid material with a flexibleadhesive base 47 that is of a compressible conductive material thatprovides for the PainTrace sensor 43 to remain in contact with theskin's surface even when the patient is moving. A fastener 49 thatsecurely holds the PainTrace sensor 43 in place is attached to a rigidarm 51 that applies pressure to the PainTrace sensor 43 to align andhold the PainTrace sensor 43 against the flexible conductive adhesivebase 47 thereby maintaining electrical contact with the skin. The rigidarm 51 is thin enough to minimally interfere with a patient's dexterityin the use of their hands but made from a rigid wire that may be bent toconform the patient's palm or other area of the body using the PainTracesensor clip 41 to align and hold the PainTrace sensor 43 to thepatient's skin. The replaceable PainTrace sensor clip 41 has a connector53 that in a first embodiment may be inserted into a receiver 55attached to a wrist, arm, leg or ankle band to position the PainTracesensor clip 41 in different locations on the body to obtain acceptablereadings. The replacement of the PainTrace sensor clip 41 is very easilydone by pulling the connector 53 out and removing it from the receiver55 as shown in FIG. 6F and then replacing the sensor clip 41 withanother sensor clip 41. The rigid arm 51 and flexible, conductiveadhesive base 47 align and hold the sensor 43 to the skin so minimaltime is needed to replace the PainTrace sensor 43 and begin acquiringPainTrace sensor data 72.

The PainTrace application 70 may further acquire impedance and othermeasurements, apply calibration algorithms to determine a voltage offsetof the left and right PainTrace sensors 43 and adjust voltagemeasurements and based on this calculated value and tolerance settings afaulty PainTrace sensor 43 may be identified and be replaced. The size,shape, and surface area of the PainTrace sensors may be determined bythe type of subject and on which body part the sensor is attached. ThePainTrace sensor 59 may be affixed to a support 61 and adhered to thehair of the animal, as shown in FIG. 6D. The measurement of the painmatrix and central nervous system activity as it relates to pain on theanimal is a unique application of the PainTrace device 14, where for ananimal that has no ability to communicate or human that cannotcommunicate, the device 14 provides vital information about the amountthat an incapacitated or non-communicative patient may be suffering frompain and the efficacy of treatment. In further embodiments, thePainTrace sensors 41 may be attached to a collar 65 that may bepositioned in a location near to the area of the body experiencing painor be worn or draped around the neck to not impede the patient'smobility but provide for constant monitoring of the patient's PainTracesensor readings 72. The monitoring collar 65 as shown in FIG. 6E, orother wearable device may further provide for additional sensors 63 tobe affixed to the collar and collect data such as a heart rate and heartrate variability, photoplethysmogram (PPG), blood pressure, skintemperature, movement, GSR, and other vital signs.

In further embodiments, the PainTrace sensor and PainTrace device may bea single PainTrace measurement device 303 in a small housing without asupport 61 or collar 65 and simply be affixed to the patient usingadhesive as shown in FIG. 6E. In some embodiments, a separate PainTracemeasurement device 303 would be affixed to the left and right side ofthe patient's body, however in preferred embodiments a PainTraceadhesive sensor device 305 would transmit data signals 72 using a wiredconnection or wireless transmitter 306 such as a Bluetooth transmitterto communicate with the PainTrace measurement device 303. The PainTraceadhesive sensor device 305 and PainTrace measurement device 303 may havea sensor holder 308 to slide or snap in sensors 310 into a housing 312.The PainTrace measurement device 303 using the PainTrace application 70may process the data signals from the PainTrace adhesive sensor device305 and from the sensor 310 on the PainTrace measurement device 303 tocalibrate the signal and determine the signal delta that provides thepain level reading 72. The PainTrace measurement device 303 may have adisplay screen 312 to display the PainTrace data 72 and/or PainTraceFactor 102 and/or have LED lights, alarm signals or other indicators 314that show a level of pain based on for example the color of a light, thevolume of a sound, or the rapidity that a sound repeats to indicate thelevel of pain as compared to the pain tolerance level 76.

Similar indicators 314 may be used on a further embodiment of thePainTrace measurement device 320 as shown in FIGS. 6G and 6H. In thisembodiment of the PainTrace measurement device 320, the left and rightside sensors 322 are releaseably attached to holders 324 that areaffixed to the device housing 326. The PainTrace measurement device 320is then affixed along the center line C of the body with the left andright sensors 322 affixed using a weak adhesive to the left and rightside of the body, respectfully. The PainTrace measurement device 320using the PainTrace application 70 of the PMD 10 processes the datasignals from the left and right sensors 322 to calibrate the signal anddetermine the signal delta that provides the pain level reading 72. ThePainTrace measurement device 303 may have a display screen 312 todisplay the PainTrace data 72 and/or PainTrace Factor 102 and/or haveLED lights, alarm signals or other indicators 314 to show a level ofpain. As with this and other embodiments of the PainTrace measurementdevice 320, the PainTrace data 72 may then be transmitted using a wiredconnection or using wireless transmitter 306 such as a Bluetoothtransmitter to a wireless receiver such as a smartphone that may alsohave the PainTrace application 70 and/or other components and featuresof the PMD 10 accessible as a software app on the smartphone or mobiledevice. The smartphone may then transmit collected data from theacquisition environment 1 to a local or remote network 12 such as withina clinical or hospital environment and/or to the BioTraceIT PMD serversystem 18. Collected data may be integrated with previously collectedPainTrace sensor data for review using components and features of thebiotrace application software of the PMD 10 where tolerance settings maybe provided to issue alerts if any sensor readings are outsideacceptable levels. Any alerts that result in actions that can be takento correct placement of sensors or the device can be displayed eithervia GUI or mobile device apps or software integrated with nursingstations or healthcare system networks. The PainTrace sensors may alsobe integrated with other medical devices and equipment such as with ablood pressure monitor as shown in FIG. 6I, where a first PainTracesensor 330, for example designated for the left side of the body, may beheld to the skin of one arm by the cuff and bladder 332 and a secondcuff 334 or band as shown in FIG. 6J may be provided to hold a secondPainTrace sensor 330 that is held to the skin on the other side of thebody by similarly wrapping the cuff 334 around the other arm. The twocuffs 332 and 334 may be wired together or use a Bluetooth or otherwireless transmitter to have sensor readings from the sensor 330 on thesecond cuff transmitted to a PainTrace device 336 that may be integratedwith the analog or digital measuring device of the blood pressuremonitor. A holder 338 may be attached to each cuff 332, 334 to providefor the sensor 330 to be slid or snapped into place to be affixed toeach cuff 332, 334 and either wet or dry sensors may be used withtightening of the cuff 332, 334 providing adequate tension to hold thesensors 330 against the skin. The PainTrace signal data 72 from thePainTrace sensors may be transmitted to a digital display console 336 ofthe blood pressure monitor that has the PainTrace application 70 of thePMD 10 installed to calibrate the two sensor measurements and determinethe signal delta to display pain level readings 72 and/or PainTraceFactor 102 values for recording with the blood pressure reading. Infurther embodiments, the PainTrace data 72 may be collected at differenttimes where a reading is collected from the right side of the patientand is stored and a second measurement is taken from the left side ofthe patient and then calibrated with the first measurement taken todetermine the signal delta and display pain level reading 72 and/or thePainTrace Factor 102.

In other embodiments the PainTrace measurement device 67 may be worn asan activity monitor such as on a wrist band 69 as shown in FIGS. 7A and7B with a PainTrace sensor device 307 that as described herein isconnected to the PainTrace measurement device 67 using a wiredconnection or wireless transmitter such as a Bluetooth transmitter. Thewrist band 69 may be adjustable to adjust the tension of the sensorand/or be elastic to securely hold the sensor in place where in someembodiments strain measurement devices may be added to the wrist band 69to measure the tension with these measurements used in calibrating thePainTrace signal data. The control interface 71 of the PainTracemeasurement device 67 may have a display screen 73 that may be a touchscreen, LCD, LED, or other type display. The control interface 71 mayalso have one or more control buttons 75 around the display or withinthe display as determined by the type of display. The control buttons 75may turn power to the device on and off, start and stop acquisition,calibrate the device, provide scrolling to review collected data, rundiagnostics tests, send alerts, and perform other functions. The display73 may show the collected signal data 77, display the PainTrace Factor102 and display other components and features of the biotraceapplication software of the PMD 10. For example, the control buttons 75and/or display screen 73 may provide for inputting data such asexercise, activities, and other information within the LifeTraceITcomponent of the PMD 10. The PainTrace sensor device 307 may have awristband 309 and electrical components 311 for the collection andtransmission of data. In an embodiment, a support 313 may provide forthe attachment of the electrical components 311 and provide for a wet ordry sensor 315 to be affixed to the support 313 using an adhesive 317.In further embodiments, the support 313 and sensor 315 may have aninterlocking connector as described herein to provide for thereplacement of the sensor 315 when using the PainTrace sensor device 307over long periods of time. In some embodiments, the sensor 315, support313, and wrist band 309 may all be disposable.

The housing 79 of the PainTrace measurement device 67 supports thecontrol interface 71 so that it is easily accessible across the wrist ofa user. The housing 79 also supports the PainTrace sensor 81 in someembodiments. The housing 79 is lightweight and of a minimal thickness asshown diagrammatically in a side elevation view in FIG. 8A. The housing79 may further be contoured for comfort and be substantially rectangularin shape to be worn across the wrist to provide for a large contactsurface area 83 of the sensor and sensor clusters as shown in FIG. 8B.In some embodiments, the sensor 81 may be a wet sensor that requires aconductive gel or adhesive 317 to be applied to the sensor or the skinduring use. For example, the PainTrace measurement device 67 andPainTrace sensor device 307 with wet sensors may be used as part of amedical physical where a HCP may prepare the sensors with conductivegel, or use a sensor that has been pre-applied with gel at themanufacturer, and may place the PainTrace measurement device 67 and thePainTrace sensor device 307 on each of the patient's wrists, palms, orappropriate anatomy on contralateral sides. After sitting quietly for afew moments, pain level and pain matrix and central nervous systemactivity data 72 and the patient's PainTrace Factor 102 may be collectedwith other BioTrace Factors collected from other sensors to be used as abaseline in a measurement of pain with other biophysical readings of thepatient.

The PainTrace sensors 81 and 315 may further be replaceable where wetsensors may be single use and used for example over only two hours whiledry sensors may be used for longer periods of time with for continualdata collection. The dry sensors for example may be replaced daily, orevery two to three days, or after a longer period of time. As showndiagrammatically in FIG. 9A, the PainTrace sensor 81 may also be ofminimal thickness and a connector support 87 may be provided toreleaseably connect the PainTrace sensor 81 to the housing 79. In anembodiment, the housing 79 supports PC Boards 89 and other electronicsfor the controller interface 71 and PainTrace sensor 81, as shown in abottom view of the PainTrace measurement device 67 in FIG. 9B. Theconnector support 87 may have left and right support brackets 91 and 93that may be installed on a base 95 within the center of the housing 79.Each of the left and right support brackets 91 and 93 may include acompression spring 97 and each compression spring 97 may have a straingauge 99 to measure pressure of the PainTrace sensor 81 against the skinof the user to determine equal pressure between two PainTracemeasurement devices 67 that are worn on each wrist of the user incollecting data measuring pain and other biophysical readings such asskin conductance. The connector support 87 may also provide a locatingpin 101 to align a sensor connector 103 within the connector support 87.

The sensor connector 103 as shown in a bottom view of the PainTracesensor 81 in FIG. 9C is positioned within the center of the PainTracesensor 81. The sensor connector 103 may have a tab extender 105 thatextends from an opening 107 in the center of the sensor connector 103 inparallel with the longer dimension of the contact surface 83. The tabextender 105 is affixed to a spindle 109 that extends to a plate 111with the spindle 109 creating an offset distance between the tabextender 105 and the plate 111. The plate 111 may be affixed to thebottom 113 of the contact surface 83 of the PainTrace sensor 81 using anadhesive or another attachment device. As shown in FIG. 10A, the bottomsurface 111 may have conductive strips 115 or other electricalconnection points to mate with the compression springs 97 as electricalcontacts or with other electrical contacts from the connector support87.

As shown in FIG. 10B, the PainTrace sensor 81 is connected to thehousing 79 using each end 117 of the tab extender 105 and the left andright connector supports 91 and 93. The connector supports 91 and 93 areformed with a vertical extension 119 and an overhang 121, as shown inFIG. 10C, with the overhang 121 of the left connector support 91directed towards the overhang 121 of the right connector support 93. Theconnector supports 91 and 93 are spaced at a distance apart that isslightly larger than the width of the tab extender 105 of the sensorconnector 103 so that the tab extender 105 may be inserted between thetwo connector supports 91 and 93. The opening 107 on the tab extender105 aligns with the locating pin 101 on the base 95 of the connectorsupport 87 and provides for the PainTrace sensor 81 to be rotated tohave the ends 123 of the tab extender 105 extend underneath theoverhangs 121 of the connector supports 91 and 93 to secure thePainTrace sensor 81 to the housing 79. The compression spring 97 of eachof the connector supports 91 and 93 compresses against the PainTracesensor 81 to push the sensor against the skin to increase contact of thesurface contact area 83 of the PainTrace sensor 81 to improve sensorreadings. The compression springs 97 may also connect with theconductive strips 115 on the bottom surface 111 of the PainTrace sensor81 to send signal data 77 from the PainTrace sensor 81 to theelectronics of the PainTrace measurement device 67. The PainTracemeasurement device 67 may display the signal data 77 within the display73 of the control interface 71 and/or transmit the data using thecommunications module 25 within the PainTrace application 70 of the PMD10 that may be installed on the PainTrace measurement device 67 or beinstalled remotely on a smartphone or other local digital device,remotely within a network 12 such as within a clinical or hospitalenvironment and/or be transmitted to the BioTraceIT PMD server system18.

As shown in FIG. 11A, in a first position prior to connection, thesensor connector 103 of the PainTrace sensor 81 is aligned in betweenand in parallel with the connector supports 91 and 93. The PainTracesensor 81 is then rotated as shown in FIG. 11B to align the PainTracesensor 81 perpendicularly to the connector supports 91 and 93 and havethe bottom 113 of the sensor contact surface 83 compress against thecompression springs 97. Alternatively, the PainTrace sensor 81 may slideinto place in embodiments of the connector without the locating pin 101.The compression springs 97 remain in tension pushing outwards againstthe PainTrace sensor 81 with the tab extender 105 under the overhang 121of the connector supports 91 and 93 securing the PainTrace sensor 81 tothe housing 79. A ridge or other protrusion 123 may be provided on thesensor connector 103 to lock the PainTrace sensor 81 in alignment withan indent 125 on each of the connector supports 91 and 93. As shown inFIG. 12A, the PainTrace sensor 81 prior to connection may extend beyondthe edges 127 of the housing 79 to provide for a user to easilymanipulate the PainTrace sensor 81 to rotate and connect the sensor 81.The edges 127 of the housing 79 may form a rim 129 to seat and align thePainTrace sensor 81 on the housing 79. The PainTrace sensor 81 may be ofa thickness slightly wider than the housing rim 129 to provide for auser to grasp the edges 131 to rotate and remove the sensor 81 oralternatively a user may simply press down in the middle of thePainTrace sensor to compress the springs 97 and separate the ridges 123from the indents 125 and turn the sensor to align the tab extender 105between the two connector supports 91 and 93 and lift the PainTracesensor 81 off of the housing 79 and/or turn the PainTrace measurementdevice 67 over to have the PainTrace sensor 81 disengage and fall out ofthe housing 79. Other embodiments may provide for the PainTrace sensor81 and 315 to snap in using fasteners and/or locking tabs that may haveextensions or buttons that may be compressed to release the sensor fromthe tabs securing the sensors to the housing 79. Other embodiments forconnection of the sensors to a housing, wrist band, collar, support orwearable or other fixture for attachment to the skin are contemplatedwithin the scope of the present invention that may also include means tohold and press the sensor against the skin to maintain conductivity.

The PainTrace measurement device 67 requires measurement from each sideof a patient with calibration between the PainTrace sensors 81 orPainTrace sensor device 307 to minimize signal noise and limit erroneousreadings. The strain gauge 99 on each of the compression springs 97 orstrain gauges electrically connected to other embodiments of thePainTrace device may provide for the pressure of the PainTrace sensor 81and 315 against the skin to be measured. The strain gauge measurementsdepending on the placement of the strain gauge on the PainTracemeasurement device 67, PainTrace sensor device 307 wrist band 69 or 309,collar 65 or other wearable may provide a marker to ensure equalpressure and tension of the sensors 81 and 315 against the skin. Asdescribed herein, the pain measurements using the PainTrace device 14are passive measurements of skin potential, contrary to galvanic skinresponse which applies a current. PainTrace device 14 measurements aretaken without applying voltage to the skin and instead measure theelectrical activity of the pain matrix response to stimuli through thedetection of voltage or current differences between a first PainTracesensor placed at a location on the left side of the body and a secondPainTrace sensor placed at a similar location on the right side of thebody. In some embodiments, the PainTrace device 14 may include a powersupply to apply voltage to the PainTrace sensors or associatedipsilateral sensor pairs attached to the device to take measurements ofimpedance and conductance and/or other passive measurements which mayalso be taken prior to, during, or after acquiring pain measurement andpain matrix activity data or at periodic intervals while collecting painmeasurement and pain matrix activity data to calibrate the readings foreach PainTrace sensor 81 or sensor cluster based on differences in skincontact, skin quality, and the effects of movement on the sensor to skininterface and additional physiological measurements. Because, thePainTrace device applies no voltage to the skin the pain measurement andpain matrix activity data may be continually collected without anyadverse effects on the patient and calibration measurements may beperformed intermittently between the collection of data to determine therequired offsets and calibrate the PainTrace device. The calibrationmeasurements may further determine sensor failure and provide anindicator to the user that the PainTrace sensors 81 and 315 must bereplaced.

As described herein using contralateral sensors that are placed insimilar locations on the left and right side of the body providemeasurements of electrical activity due to neural transmissions that maybe both to and from the brain in reaction to locations of pain withinthe body. The contralateral measurements of the voltage differences fromthe PainTrace device 14 correlate well with the ratings of pain that apatient may offer such as in comparing the measurements to ratings onthe Visual Analog Scale (VAS). In some embodiments the PainTrace device14 may combine contralateral sensors with ipsilateral sensors on one orboth sides of the body to provide additional information of electricalactivity within the body. The ipsilateral sensors may acquiremeasurements passively or actively to for example acquire galvanic skinresponse GSR at locations similar to the contralateral sensors. Datafrom ipsilateral measurements may be used to calibrate and improve thesignal to noise ratio of the contralateral pain measurements reading.Data from the ipsilateral sensors may further be correlated with thecontralateral readings to validate the pain measurement readings whererecent studies have shown that increased electrical activity on one sideof the body may be related to pain, stress and anxiety.

In an embodiment the PMD includes one or more PainTrace sensors and/orone or more other biophysical sensors that may be arranged in a housing350 to be installed and remove from the PainTrace Device, a wearable, oranother measuring device to have the grouping of sensors be placed onthe body at similar left and right locations. In one embodiment thesensor cluster may include a single contralateral sensor 352 and a pairof ipsilateral sensors 354. In other embodiments, the contralateralsensors and ipsilateral sensors may each be in separate housings and beseparately placed at locations on the body. For example, a contralateralsensor may be placed on each of the left and right clavicle and twoipsilateral sensors as a pair may be placed on the palm of each hand orat other locations that align along the left or right axis of the body.

In an embodiment of a sensor cluster as shown in FIG. 13, the housing350 supporting the sensors may be of a flexible material to fold orslightly bend to adapt to movement and positioning of the skin. A border356 that may be prepared with conductive gel or that has pre-applied gelsurrounds the sensor surface 358 of the housing 350 to removably adherethe sensor cluster to the skin. Sensor clusters having both ipsilateralsensors and contralateral sensors may be placed at similar locations oneach of the left and right side of the body. The ipsilateral sensors 354are connected across a load resistor 360 of between 0.5 k to 900 k Ohmsand preferably 22 k Ohms. The contralateral sensors 352 are alsoconnected across a load resistor 362 by electrically connecting the leftand right sensor clusters. In connecting the contralateral sensors 352,a lead 364 may be of any length with an electrical connector 366, thatmay be in the form of a clip, snap, dual pin fastener, or other typeconnector. The lead 364 may extend from each sensor cluster to beconnected after the sensor clusters have been placed at a location onthe body such as the hypothenar or thenar region of the palm of eachhand. To close the circuit between the contralateral sensors 352, theconnectors 366 from the left and right sensors may simply be connectedtogether. However, in some instances having a wire across the body maybe uncomfortable or awkward for the patient. The connectors 364 maytherefore in some embodiments be attached to an article of clothing,each bed railing, or another object that electrically connects the twosensor leads to close the contralateral sensor circuit and still providefor patient mobility and use of the hands. In some embodiments, the leadwire may have a USB type connector to be plugged into a wearable that isplaced around the wrist or neck of the patient. The wearable may be inthe form of a wireless activity tracker and may include the circuitryshown in FIG. 13 to collect and transmit data from the sensor clusters.Alternatively, the circuitry is contained in the separate handheldPainTrace device 14 that may include wireless transmission or a dataoutput line in the form of a USB cable to transmit and download painmeasurement data collected from the PainTrace sensor clusters. In otherembodiments, the circuit may be included with each sensor or sensorcluster.

In some embodiments, the PainTrace device 14 of the PMD may not havecontralateral sensors connected with a wire across the body but insteadhave two pairs of ipsilateral sensors each placed contralaterally to theother. Passive and active measurements may be from each pair ofipsilateral sensors separately and/or simultaneously and the signalsfrom these readings are combined to determine pain matrix activity andother biophysical measurements. The ipsilateral sensor pairs that areplaced on similar locations of the body may be placed on the wristswhere in some embodiments the PainTrace device 14 may be incorporatedinto an activity monitor and a first activity monitor is placed on theleft hand wrist and a second activity monitor is placed on a right handwrist to acquire pain measurements.

In embodiments of the PainTrace sensor circuitry of the PMD, thecircuitry as shown may include signal processing 370 and band passfilter circuitry 372 to improve the signal to noise ratio and quality ofthe signal. A microprocessor 374 and timer 376 to control thecollection, sample rate and transmission of the signal and an A/Dconverter 378 for converting the measured EDA or other analog signals todigital signals. Software applications, control programs and calibrationalgorithms such as the iterative linear resistance calibration may bedownloaded or transmitted to the circuitry using wireless communicationcircuitry 380 and or a wired connection and be stored and accessiblefrom data storage 382 and memory 384 within the circuitry. The circuitrymay include an output display 386 or data may be displayed on an outputdevice remote from the circuitry through wired or wireless datatransmission.

Using both ipsilateral sensors 354 and contralateral sensors 352provides for a signal comparator 388 to evaluate signal characteristicsincluding voltage, current, frequency, linearity, and amplitude and usethese measurements to calibrate and adjust the voltage or current of oneof the left ipsilateral sensor signal, the right ipsilateral sensorsignal and/or the contralateral sensor signal as prescribed by thecomparison of signals. As shown in FIG. 13, output leads from the loadresistor 360 are connected to an amplifier where in the embodiment ofthe circuit shown a first amplifier is designated as AMP 1 with theidentifier 390 for the left ipsilateral sensors 354 a second amplifieris designated as AMP 2 with the identifier 392 for the right ipsilateralsensors 354 and a third amplifier AMP 3 with the identifier 394 isconnected to the output leads of the load resistor 362 for thecontralateral sensors 352. The load resistors of each sensor or sensorcluster may in some embodiments be variable resistors in order tocalibrate the circuitry and adjust voltages and current flow. Forexample, in calibrating the contralateral signal, a variable loadresister 362 may be used and a comparison of the contralateral signal tothe signal measured from either or both of the left and rightipsilateral sensors may be made. From characteristics of the signalsdetermined by the signal comparator 388, the variable load resistor 362as shown in this example may be adjusted to boost components of thesignal and/or remove outliers that may be related to movement or othersignal interference. The band pass filter may further be adjusted asnecessary to one or more optimal frequency ranges to remove signalnoise. PainTrace sensor circuitry of the PMD may further include a powersupply such as battery 368 to apply voltage across the load resistors.For example, calibration steps may include applying a voltage across theload resistor 362 of the contralateral sensors 352 and/or the loadresistors 360 of each of the pairs of ipsilateral sensors 354 to verifyan electrical connection and/or to determine the skin conductivity.Using a skin conductivity measurement from each sensor, differences inskin contact, skin quality, movement, and the other effects of thesensor to skin interface and physiologic measurement may be identified.Large differences in these measured values may indicate a faulty sensoror limited contact of the sensor surface to the skin. For smallerdifferences in impedance within specified tolerance levels, thePainTrace application 70 of the PMD 10 may apply calibration algorithmsto add or subtract an offset based on the difference in impedance tonormalize voltage measurements between the left and right contralateralsensors or pair of ipsilateral sensors.

Using the PainTrace device of the PMD, data is collected withoutapplying voltage to the skin in order to measure pain matrix activity ofthe patient. However, by applying a voltage to ipsilateral sensorsplaced on wither the left or right side of the body, the galvanic skinresponse GSR may be measured. The PMD uniquely combines and normalizesbiophysical measurements such as GSR, HRV, blood pressure, pulse,movement, skin temperature, and other signal data with pain matrixactivity data collected using the PainTrace device 14. Through the PMDanalysis, the measurement of pain matrix activity may be correlated on atime scale to evaluate peak activity of GSR that may be related toemotional response and points of increased levels of pain. As shown inFIG. 14, simultaneous measurements using ipsilateral sensors located onthe fingers of the right hand to measure GSR, and pain matrix activityusing the PainTrace device 14 with contralateral sensors placed on thethenar region of the palm of each hand, pain matrix activity is measuredover a period of time. The cold pressor test, a standard method forinducing experimental pain, was conducted during a portion of thisperiod. (Walsh et al. Normative Model for Cold Pressor Test. AmericanJournal of Physical Medicine and Rehabilitation. February 1989; 68(1):6-11). Using the PainTrace application 70 of the PMD 10 and adjustingthe time block 78 to hours and minutes data collected over a continuousperiod of time may be reviewed. The PMD correlates measurements of theGSR readings 395 and PainTrace data 396 and displays the pain stimuluspoints at 25 minutes 398 and at 32 minutes 399. The PainTrace Factor 102or other BioTrace Factors 150 may be added to points in the time periodfor additional information. For example, the addition of the PainTraceFactor 102 may be completed by dragging and dropping the PainTraceFactor icon 102 within the time period. Alternatively, an option to addthe PainTrace Factor 102 and other BioTrace Factors 150 through a menuor other application interface may be provided to be displayed such asdisplaying the PainTrace Factor 102 at maximum points of deflection asshown by the dotted line arrows within the display. Other biophysicalmeasures such as heart rate variability may be individually displayedfor the acquisition by simply dragging and dropping the HRV icon 302into the time period.

The PMD 10 provides for a review of integrated data or individualdisplay of the GSR and pain matrix activity which in this exampleexhibits an inverse relationship prior to the introduction of the painstimulus. Over this time period, simultaneous readings were taken withthe GSR device being turned on and off at two minute intervals todetermine how the introduction of current effected the PainTrace device14 measurements. GSR cycling was conducted prior to the 25 minute timepoint in the experiment when the noxious stimulus 398 was introducedafter which point in time a consistent GSR measurement was utilized.Fluctuations in PainTrace data 396 dissipated when the GSR device wascycled for longer periods increasing from two to a longer three-minutecycling frequency. Starting at the 25-minute time point the cold pressortest, which consisted of immersing the right foot in an ice bath for 1.5minutes, is initiated demonstrating a negative deflection of the painmatrix signal through 26.5 minutes followed by a recovery period to anon-pain state at 32 minutes when the cold pressor test was repeatedagain demonstrating a negative signal deflection denoting a pain statefollowed by a recovering period until 41 minutes. From the PMD displaythe correlation of GSR to pain matrix activity shows that during painfulstimuli the GSR and pain matrix signals are not synchronous butdemonstrate a direct relationship unlike the initial inverserelationship prior to the introduction of pain stimulus. Using the PMD10, contralateral and ipsilateral sensor data is utilized to calibrateand further discern pain matrix activity enabling a greaterunderstanding of differentiation between various contributors to theindividual pain experience.

Using the PMD 10, the analysis, correlation and transformation of datafrom multiple biophysical measurements allows for brain activity withinthe pain matrix and patient susceptibility and experience of pain to bebetter understood. The difference in response evidenced by simultaneousGSR and PainTrace measurements creates additional information regardingvariability between brain region activity in the pain matrix,sympathetic response, and emotional processing which are componentsrelated to the individual experience of pain. Similarly, the PMD 10provides for heart rate variability to be simultaneously measured andcorrelated to determine parasympathetic nervous system activity levelsand the relation of vagal tone. (Farmer A et al, Psychophysiologicalresponses to pain identify reproducible human clusters. Pain. 2013November; Volume 154 (11): 2266-2276). Vagal tone has been evidenced torelate to endogenous endorphin release in response to the presence ofpain and therefore measurement of parasympathetic nervous systemactivity and related vagal tone are important factors to transformingphysical biosignals into quantitative and objective measures of the painmatrix and central nervous system activity levels reflective of bothstates of pain and health and for use as a tool in diagnosis andidentifying underlying sources of medical compromise. (Kollarik M etal.Vagal afferent nerves with the properties of nociceptors. AutonNeurosci. 2010 Feb. 16; 153(1-2): 12. Published online 2009 Sep. 13.doi: 10.1016/j.autneu.2009.08.001). In addition to the diagnosis ofpain, the PainTrace devices 14 of the PMD 10 provide early diagnosis ofintestinal distress, allergies and respiratory infection, sports injuryrelated to tendon and ligament damage, as well as diagnosis of chronicpain related to back injury, dental and migraine cases among others.

In further embodiments sensors or sensor clusters may be sewn orremovably attached to clothing or fabric pieces using a flexible sensorholder referred to herein as PMD sensor track 400. The PMD sensor track400 is a flexible sensor attachment device comprised of an extendedstrip 402 of plastic, metal or another material that may be formed witha U-shaped channel, an I-beam track, a T-shaped track, or in someembodiments be a flattened piece with openings for the attachment of aseries of sensors or sensor clusters, or a matched contour channel. Asshown in FIG. 15A, the PMD sensor track 400 may support electroniccircuitry which may be within an enclosure 404 or provide an electricaloutput port 401 such as a USB in a mini or micro size for the attachmentof the PMD sensor track 400 to external electronic circuitry. In otherembodiments, the PMD is accessed remotely through wireless communicationcircuitry within the enclosure 404 Bluetooth, NFC, or other types ofwireless communication protocols. The PMD provides for the acquisition,control and communication to and from the attached electrodes andsensors of the PMD sensor track 400. The PMD circuitry also providesinitialization to detect when sensors are added or removed from the PMDsensor 400 and associate the electrodes and sensors along the strip 402with a specific patient, HCP, physician, and a clinical or hospitalnetwork as described herein. The PMD sensor track 400 may include apower supply 406 or battery to power sensors and apply voltages forcalibration of sensors. In some embodiments, the power supply 406 mayprovide a float current to the electrochemical capacitor of one or morePainTrace sensors to improve energy, power characteristics andsensitivity.

A Velcro or a hook and fastener fabric strip 408 may be providedcontinually or along portions of the upper or lower surface of the PMDsensor track 400 to flatly adhere the strip to a piece of clothing orfabric. In some embodiments, a strip of adhesive may be provided as welleither continually or partially along the upper and/or lower stripsurfaces to connect the PMD sensor track 400 to the skin or hair of ananimal. Along or beneath the Velcro and/or adhesive strip 408,conductive metallic strips 410 that may be electrically connected to thePMD circuitry through a direct or remote wireless connection areprovided. The conductive strips 410 may also be electrically connectedto communication connectors 411 installed in locations along the strip402 of the PMD sensor track 400. The communication connectors 411 may bedual or multi-pin, mini or micro-USB, or other types of electricalconnectors suitable to accommodate the data transmission andcommunication requirements of the sensors, electrodes and PMD circuitry,PainTrace devices 14, other biophysical devices 11 and components andfeatures of the PMD 10.

The communication connectors 411 may be positioned at a single or atmultiple locations along or at the beginning or end of the PMD sensortrack 400. The electrical connectors 411 may provide for PMD sensortracks 400 to be interconnected to add or remove sensors to increasediagnostic capability as needed. A shown in FIG. 15B, the PMD sensortrack 400 may have a series of male connectors 413 and a series offemale connectors 415 so that an electrical wire 417 such as a micro USBcable may be used to connect one PMD sensor track 400 to another. Inother embodiments, as shown in FIG. 15A, a sensor cluster 419 may beconnected along a portion of the length of the PMD sensor track 400. Inother embodiments, an additional PMD sensor track 400 may beelectrically connected using an end plug 421. A first end of the PMDsensor track 400 may have a male end plug 421 and the second end mayhave a female end plug 423 to electrically connect a series of PMDsensor tracks 400 together as needed. In order to communicate andcontrol sensors of different types, the conductive strip 410 includes aseries of locator pins 425 that detect and relay a signal when a sensor412 is attached to or detached from the PMD sensor track 400 at thatspecific location. Embedded software within the PMD circuitry identifiesthe type of sensor, the acquisition requirements and other parametersand provides communication protocols to set time and sample rate fordata acquisition.

In some embodiments, a sensor 412 is installed to the PMD sensor track400 by sliding the sensor fastener 414 into and along a U-shaped channel416 having left and right support rails 418 as shown in FIG. 15B. Thesensor fastener 414 may have a flattened top surface 420 and wingedextensions 422 with a rounded base 427. The winged extensions 422 aresupported on the left and right support rails 418 and the flat uppersurface 420 provides for an electrical connection to the conductivitystrip 410 to be maintained as the sensor 412 is compressed flat as theattached clothing or fabric is tightened and compressed against theskin. The rounded base 427 provides for movement of the sensor fastener414 within the U-shaped track as the rounded base 427 along the wedged,curved or slanted edges 429 of the channel rails 418 rollsperpendicularly to the rails 418 and slides along the rails 418 as thesensor 412 is compressed to the skin. By forming the fastener 414 with arounded base 427, the surface 446 of the sensor 412 remains in contactwith the skin as the PMD sensor track 400 and/or clothing is compressedto the skin or as the patient moves while the PMD sensor track 400 isattached.

In another embodiment, the PMD sensor track 400 may be a flattened strip430 with a series of female parts of a press fastener 432 aligned andsecured through openings in the strip 430 as shown in FIG. 15C. Thesensor 434 will have a male part press fastener 436 to be inserted intothe female part of the press fastener 432 and be secured to the PMDsensor track 400. The female and male press fastener parts may be of aconductive material and electrical strips 410 may be provided totransmit and receive signals from the sensors 434. A Velcro or adhesivestrip 408 may be provided along the flattened fastener strip 402 of thePMD sensor track 400. The sensor fastener 436 may be of a rounded shapeto roll within the opening and prevent movement of the patient or PMDsensor strip 400 from pulling the sensor 430 away from the skin. Inother embodiments, the sensor fastener may be a partial oval shape toslide over the rails of an I-beam or T-shaped track or of any shape thatprovides for the sensor to be correctly oriented and the fastener 436 tofreely move within the connection to the strip 402 to prevent the sensorfrom tipping and being pulled from the surface of the skin duringmovement. Other fasteners and track shapes and dimensions arecontemplated within the scope of this component of the PMD system 10 ofthe present invention.

The sensors 412 may be positioned in optimal locations along the PMDsensor track 400 with respect to the area on the body being measured,the size of the person, the clothing worn, the amount of time thesensors 412 will be used, the type of sensor 412 being used and otherfactors. A range of sensors of different capabilities and electricalrequirements may be provided with the power supply or battery 406supplying power as needed. In some embodiments, the sensors may bepermanently affixed to the PMD sensor track 400, using adhesives,staples, thread, clips, snaps or other fasteners. In some embodiments,the PMD sensor track 400 may be disposable. As shown in FIG. 15A, theextended flexible material of the PMD sensor track 400 provides forbending and shaping the strip 402 in order to properly place sensors orsensor clusters in proper location to acquire pain matrix activity data,EDA, PPG, HRV, GSR and other biophysical information. For example, thePMD sensor track 400 may provide for separating two ipsilateral sensors440 along each side, position contralateral sensors 442 in similarlocations, and support a PPG monitor with all of the data collected andanalyzed within the PMD system. The PMD sensor track 400 may be securedwithin a shirt using the Velcro strip 408 to wrap the PMD sensor track400 around the neck and shoulders and affix the sensors along theclavicle and chest for readings. The flexibility of the PMD sensor track400 contours the surface 446 of the sensor 412 to the irregularities ofthe skin or hair of an animal. An adhesive conductive gel layer may beprovided on the surface 446 of each sensor 412 to adhere the sensor tothe body.

In a further embodiment, the PMD sensor track 400 may be used withcompression clothing or fabric such as with an elastic bandage, athletictape, bandeau or other article of clothing to align the PMD sensor track400 on a location around the arm, leg, or torso of the body and compressthe sensors to the surface of the hair or skin. In this manner there maynot be a necessity for gels or adhesives on the skin to hold andmaintain continuity of the surface 466 of the sensor to the skin tooptimize readings. The fabric of the elastic bandage or article ofclothing may be tightened to the body to compress the sensors on theskin using Velcro or other fasteners. As part of the PMD system thatintegrates data from numerous sensors and references, the PMD sensortrack 400 provides for multiple sensors and sensor clusters to be easilyconnected and aligned to the skin to improve the continuity of eachsensor and overall data acquired from the PainTrace and otherbiophysical sensors.

In further embodiments, the dosage of pain medications may be evaluatedbased on individual PainTrace Factors 102 and direct measurement of thePainTrace device 14 before and after administration of a painmedication. Pre and post-administration PainTrace Factors 102 willprovide efficacy data based on dosage, and by monitoring over time canevaluate tolerance and the need to evaluate alternate interventions toprovide an individualized pain management regimen.

In further embodiments, the tolerance threshold for pain or from othersensor readings may be used for the administration of medication throughfor example an automated pump dispenser. Limits on dosage and timebetween administration of the medication may be set and then based onthe data collected from the pain measurement device, the pump maydispense medication when sensor readings exceed pain tolerance levelsettings. Particularly, for an incapacitated patient the automatedmedication delivery system using the PainTrace sensor readings may proveeffective to control and maintain levels of medication as needed. Asshown above, the administration of medication and pain levels may betracked and reviewed to determine the efficacy of treatment using thePainTrace Application 70 and other components and features of the PMD10.

In a further embodiment of the present invention, the PMD 10 mayidentify patients at high risk for dependency on medication. ThePainTrace sensor data may be used in a unique way to prevent the abuseof medication by controlling when a patient has access to theirmedication based on the pain matrix activity and pain tolerance readingscollected. In a first embodiment, a secure pill box, or other medicationdispenser may be locked using an electronic security code. The patientmay be given an identification code to unlock the pill box, however thissecurity code may be overridden by the PainTrace sensor readings whenthe sensor readings are well below the pain matrix activity and paintolerance levels for the patient. Once tolerance levels are exceeded,the lock is activated and the patient may enter their identificationcode or alternatively simply open the pill box. Another embodiment isthat if appropriate pain matrix activity and pain tolerance levels aremeasured the patient would receive single-use passcode via the mobiledevice app to open the pill box a single time and then the passcodewould be reset. In this way the amount of medication taken by thepatient may be controlled and only be accessible when pain levels are atappropriate levels and require treatment. Timers integrated with thesecure pill box could further prevent access to the medication prior toa set time limit in order to have prescribed time intervals between theadministrations of medication. Healthcare provider goals and painmanagement agreements could be integrated into the system.

The components and features of the PMD 10 provides biological dataspecific to the patient and combines this information with the PainTraceapplication 70 data. This information may be presented within theBioTraceIT component 60, as shown in an embodiment in FIG. 16, throughother components of the PMD 10 and/or through another patientinformation application. For medical personnel, the BioTraceIT componentapplication 60 may display a diagrammatic human representation 122 ofthe patient based on the biological data. The diagrammatic humanrepresentation 122 may not provide any identifying features, but forverification and analysis, it may assist the HCP with the generalcharacteristics of the sex, shape, and size of the patient. Thediagrammatic human representation 122 may further provide a painlocation indicator 124 to allow the HCP to quickly verify the region ofdistress. For example, a shorter patient with larger features based onthe weight, height and body mass index (BMI) with a pain in the leftknee is shown in FIG. 16. The name and other identification informationof the patient may be provided in some embodiments, in furtherembodiments to protect confidentiality of the patient identifier code126 may be provided to distinguish the patient record from otherpatients. General biologic data may be listed in a table 128 with labelsand values describing physical features of the patient. The biologicdata may further include psychological evaluations 130, social data 132,medical history 134, recent travel 136 and/or any other information thatmay be relevant to diagnosis and treatment may be included within thepatient data. The data may further include data that may be consideredunrelated to diagnosis and treatment such as data related to economicstatus 138 and insurance coverage 140 to be used within the MediTraceITcomponent 64 of the PMD 10. If available, or using features of the PMD10 information may be added, including data from other pain measurementsor ratings such as the Visual Analog Scale (VAS) for comparison with theobjective PainTrace Factor 102. The PMD 10 provides for the display tobe customized so that different factors may be selected beyond a corefactor template based on advanced user options and preferences.

The data may be integrated with the PMD 10 through electronic healthrecords or through survey information from patients. If available,patient records are uploaded from an Electronic Health Record (EHR) andare associated with the Patient Identifier Code 126 that links thepatient's health records to the LifeTraceIT application 60 or otherpatent data application. If the EHR is not available, the patient may beprompted for pertinent information such as age, height, weight,comorbidities, and other information. The patient may further beprovided with a Consent Form that informs the patient of how this datawill be used, privacy policy, and terms and conditions with respect tothe sharing of their data that will be utilized to improve thehealthcare communities understanding of a particular healthproblem/disease state and to improve diagnosis and treatment. ThePatient Privacy policy may present information on the legal and ethicalresponsibility to safeguard patient privacy and the privacy of allpatients and protect the confidentiality of their health information andmedical records. These health records may include information about testresults from blood samples, physical examinations, medical history andany other data collected or reviewed during the course of your treatmentfor the patient. The confidential information may also include personalinformation such date of birth, as well as medical records from aprimary care physician where any health information that could be usedto identify a patient is called “Protected Health Information” (PHI).The BioTraceIT PMD server system 18, outside of any institution, keepsthe patient anonymous and instead has only the objective of looking atlarge groups of individuals to better understand health challenges andimprove patient outcomes. In requesting patient data for use within thesoftware application, the PMD 10 may require acknowledgement ofacceptance by the patient to use the data beyond use in the acquisitionof data from the PainTrace sensor 14 and other medical devices. TheLifeTraceIT application 60 or other patient data application may furtherprovide access to the survey information 144 submitted by the patient tothe physician. Features of the PMD 10 may further provide access toprior medical records 146 of the patient and to a data entry application148 for the physician to enter notes on diagnosis and treatment. Thepatient survey may provide for a patient to create a personal healthrecord that they can access through their electronic health record viathe hospital network 16, or through a separate software applications asavailable options for the patient to elect, providing for the patient totrack treatment and access reference materials related to their diseasestate.

The patient survey may have a series of questions, that the PMD 10 mayiterate and direct to particular questions based on the receivedanswers. In this manner, the patient will be stepped through screens toanswer questions pertinent to their particular health problem, symptoms,emotional state and disease state. In the most basic example, a firstquestion pertaining to whether the patient is male or female thesoftware will present a question on pregnancy in the female survey, butnot in the survey presented to a male patient. The survey questions mayrelate to basic demographics, specificbehavioral/environmental/psychological/social factors, specificshort-forms and developed questionnaires for both the evaluation ofcertain parameters and correlation to existing data already gathered viawidely utilized assessment tools, such as assessment questionnairesand/or tools related to pain that may include: SF-MPQ; BPI-SF; TOPS;SF-36; WHYMPI; VAS; PGIC; NRS; and others. The questions and surveysincluded to gather data are stored to be used periodically to possiblybe given to the patient again to re-evaluate correlations betweenBiotrace Factors as treatments and outcomes are further understood.

The survey may include general questions on age, gender, ethnicity,height, weight, and occupation to provide baselines and establish thepatient within a general population of patients. The survey may then askmore specific and immediate questions to determine current physiology,psychological state and symptoms that as example questions may be asfollows with specific selection box, rating scales, or data entry boxesfor the patient to respond: In the past seven days. In general, howwould you rate your physical health?

Excellent

Very Good

Fair

PoorIn general, how would you rate your mental health, including your moodand your ability to think?

Excellent

Very Good

Good

Fair

PoorIn general, how would you rate your satisfaction with your socialactivities and relationships?

Excellent

Very Good

Good

Fair

PoorDo you exercise? How often?What if any exercise or high level of physical activity did you completein the last 48 hours?Do you take any medications? What?Have you experienced a recent injury? If yes, please explain:Do you have any continuous or regular pain that you experience on adaily basis? If so. Where?How long have you experienced this pain?Assessment using VAS: Please rate your current level of pain if any onthe scale below.Have you experienced, or currently are experiencing any of thefollowing:A list of disease states such as cancer, stroke, heart attack, surgeryOther general health questions may be taken from a standard healthsurvey such as the SF-36 Health Survey. All answers are compiled andassociated with the patient or code for the de-identified patient andare presented within the LifeTraceIT component application 60 or otherpatient data application by the PMD 10.

The data may further be linked to the BioTraceIT analysis application 62for a HCP to access patient diagnostic readings (e.g. pain levels),analyze those readings, and see factors that may contribute to elevatedor suppressed readings (e.g. age, weight, comorbidities, etc. may affectpain levels). The administrative tools module 21 of the PMD 10 mayprovide access to specific information to be controlled by anadministrator, so that a physician may be provided access to all patientinformation, while another HCP may through a login and password beprovided with only test results, medication, or treatment informationspecifically as necessary and related to their interaction with thepatient.

As shown in FIG. 16, the physician or HCP with proper administrativeaccess may review the biological data 128 and select any factors thatthey believe are relevant in diagnosis using check boxes 149. Thesefactors referred to herein as the BioTrace Factors 150 are also analyzedusing statistical and comparative algorithms within the data analysismodule 27 in relation to populations and disease states based onreference materials and accumulated patient data. In general, the PMD 10will have an evolutionary nature, in that it will constantly be updatedwith data input from health care providers who are gathering“BioTraceIT” data on patients suffering from various disease states andwith reference materials 22 from medical journals and periodicals basedon particular disease states found within the population of patientsproviding data. In an embodiment, the PMD 10 gathers data related toacute and chronic pain that are comprised from biological,psychological, and social measures, and other relevant fields andcombines this data with an acute or chronic disease state, and with thediagnostic PainTrace data and other accumulated data points. The PMD 10integrates the gathered data in a HIPAA compliant manner, or in anappropriate fashion to protect patient privacy rights, in order toparallel and integrate data on patients using a biopsychosocialplatform, or one that comprises other appropriate factors for datapoints, to further increase the understanding of a disease state. Forexample, the PainTrace data measuring the manifestation of pain in thenervous system may be combined with data regarding biological,behavioral, environmental, psychological, and social factors todetermine the impact of these factors on the level of pain experiencedby the patient. As shown in FIG. 17, an analysis of the Biotrace Factors150 may be provided through a comparison first of general factors 152 toa population similarly situated such as patients of the same age, sex,race and other similar Biotrace Factors that may be relevant such aspatients experiencing a similar location of pain. The populationBiotrace Factors 154 may be presented as a range of values such asacceptable blood pressure and heart rate readings. The data analysismodule 27 of the PMD 10 compares the patient's Biotrace Factors 150 tothe population Biotrace Factors 154 and further performs a globalanalysis of how the patients biological data may relate to others todetermine a Factor Impact level 156 on a scale 158 of for example 1-5and indicators 160 are presented to display a level of impact that apatient's Biotrace Factor 150 might have in order to assist the HCP inunderstanding the importance and potential concern and need forintervention related to the Factor. For example, a Body Mass Index (BMI)that exceeds 40 indicated as 153 and shown within the general PopulationBiotrace Factors 154 may have the highest Factor Impact level 5 asindicated by 155 to warn the HCP of risks due to obesity. The dataanalysis module 27 identifies the Biotrace Factors 150 having thehighest Factor Impact levels 156 and performs searching of knownreference materials related to these factors to determine a ContributionFactor 162 that is a statistical percentage estimate of how much aBiotrace Factor 150 may influence a patient's perception of pain asaugmented or diminished to account for the subjective nature of pain.The data analysis module 27 further performs a comparison of PainTracedata signals 72 and PainTrace Factor 102 of the similar population andwith the determined Contribution Factor 162 to calculate the PainTraceFactor 102 as a percentage of variation between the pain matrix responseto stimuli and what the patient experiences; considering thebiopsychosocial evaluation of pain. By deriving the PainTrace Factor 102from pertinent patient demographics an evaluation and response tostandardized noxious stimuli with respect to current assessment toolssuch as VAS may provide for more valid and objective pain readings.PainTrace Factor values 102 with respect to the VAS may be made withcomparisons of female vs. male; young vs. elderly; VAS equal to 1-3 vs.VAS equal to 3-6 vs. VAS equal to 7-10 to determine the relationship ofthe PainTrace Factor 102 to the VAS. However, unlike the VAS, thePainTrace Factor 102 is adjusted by any pre-existing conditions such assurgery in the past 3 months or diabetes for the past 3 years that willaffect the normalization of diagnostic readings in comparison to thepatients Biotrace Factors 150. The PainTrace Factor 102 may further beused to establish an initial pain tolerance level 168. While the initialpain tolerance level 168 may be adjusted for the patient as data iscollected, the baseline provides for comparisons and analysisparticularly for patients that are non-communicative or for animals. ThePMD 10 may further perform a comparative calibration on output data fromthe PainTrace device 14 and set an offset 166 for voltage readings toproperly determine pain measurements.

From the comparison of general Biotrace Factors 150, Factor Impactlevels 156, Contribution Factors 162, and the Population PainTrace Data164 large amounts of data are statistically structured providing for thePMD 10 to perform analysis and comparison of the most well suitedmembers of the selected population first. The PMD 10 may first reviewpain measurements from the Population PainTrace data 164 for membershaving the same general population Biotrace Factors 154, similar FactorImpact levels 156, and related Contribution Factor percentages 162 asshown in FIG. 18. From the selected population having these statisticalsimilarities, the PMD 10 performs data analysis of the diagnosis andtests performed for a particular disease state 170. The PMD 10 furtherperforms data analysis of the efficacy of treatment 172 of this selectedpopulation. The PMD 10 compiles these analyses in summary sheets thatprovide highlights of similar diagnosis and outcomes. The informationcollected is then combined with patient test results 174, patientPainTrace data 176 and related reference materials 178 and a BioTraceIT180 is generated for analysis by the physician in the BioTraceITcomponent application 62. As shown in FIG. 19, a BioTraceIT 180increases the understanding of various disease states via amulti-dimensional data analysis platform derived from the statisticalcomputations of the physiological readings and the diagnostic relevanceof the BioTrace Factors 150. As described herein, BioTrace Factorgroupings may be developed based on general traits such as age, sexrace, disease states if known, but once identified differences withinthese populations may be extracted using the impact levels, andcontribution factors. From the selection of patients that exhibit highlevels and large contributing factors, an analysis of pain trace dataand PainTrace Factor values 102 and treatments within this population,can assist a HCP in the development of test protocols, diagnosis andtreatment for the patient. The BioTraceIT provides the HCP with asummary and of this analysis. The efficacy of treatment may then beanalyzed. The BioTraceIT component application 62 provides analysisthrough a biological tier and through a clinical tier. The biologicaltier analysis as described above and shown in FIG. 18, analyzes thecombination of the Patient BioTrace Factors 150, the PhysiologicalReadings from the PainTrace device 14 or other sensors and ContributingFactors 162 related to a knowledge base of acute and chronic diseasestates. This biological tier is focused mainly on the patient's health,history, lifestyle as it relates to similarly situated populations,physiological readings and the BioTrace Factors 150 that contribute toalter an individual's subjective perception of pain. The biological tierfunctions to translate the subjective into objective data via theanalysis of the contributing factors. The resulting PainTrace Factorvalue 102 may be further compared to the VAS or other objective measuresto improve the overall accuracy of the normalized perception for pain ofthe patient.

The clinical tier of the BioTraceIT component application 62 provides ananalysis of the combination of symptoms, the clinical data, andtreatment protocols. The clinical tier is focused mainly on exhibitedsymptoms, test results including blood and urine based analysis, andassociated treatment protocols. The combination of the Biological Tierand Clinical Tier allows for objective physiologic data in complexdisease states to aid in the analysis of potentially successfultreatment protocols and proof of efficacy based on improvements relatedto objective measurements. The PainTrace device 14 objectivemeasurements of pain provides data to evaluate efficacy and drive futureuse of treatment protocols based on patient populations, acute andchronic disease states, and contributing factors that affect subjectiveexperience of individual patients.

The BioTraceIT application 62 provides access to all pertinentinformation through the patient data icon 106, drop down menus, tabs,and/or other software features. Within a drop down menu, the BioTraceFactors 150 may be listed in order of relevance which is based onanalysis of a Biotrace Factor value as it relates to the Factor Impactlevel 156 to derive the Contribution Factor 162. The greater the valueof the Contribution Factor 162 the higher that Biotrace Factor 150 islisted in the drop-down. A Biotrace Factor 150 may be chosen from adrop-down menu and be dragged and dropped into the display to evaluatethe Biotrace Factor 150 as to its relevance to the patient's disease andsymptom experience. Further resources and information can be accessed toprovide data, explanations, research, and relevant treatment options byclicking through subsequent depth of information. A visual review of thepatient Biotrace Factors 150 and relevance is developed for quickanalysis of what will best improve a patient's health by understandingthe individual patient's health background and particulars that mostimpact the patient's symptoms that will lead to improved outcomes.

Within the BioTraceIT component application 62, the analyzed datarepresentations may be represented by variations in size, shape andcolor of icons as shown in FIG. 19. The size of an icon may representlarger patient populations and/or more common symptoms. The HCP mayclick larger icons first to review obvious factors that are initiallyeasy to address such as stress 190 contributing to TemporomandibularJoint Disorder (TMD) where patient and diagnostic information may beprovided in a dialog box 192. The Biotrace Factors 150 are evaluatedusing unique statistical algorithms to present correlations between thepatient biophysical state, disease state, medical history, referencematerials and using other sources to identify significance of onediagnostic constituent such as stress, how the constituent may relate tothe patient's pain and any relationship, contributing factor or outlier,that may require further analysis to determine or confirm the patient'sdiagnosis and treatment. The BioTraceIT Application 62 may presentpatient age 194 as a factor, the patient's medical history such as theidentification of a sport's injury 198 within the region of pain, andobesity information 200, as an example. Each diagnostic constituent maybe presented using unique combinations of elements within the display torepresent rare contributing factors or rare symptoms for patient in forexample smaller icons, and more frequent prevalent factors in largericons. By displaying size and color relationships between these BioTraceFactors 150, an HCP may validate diagnosis with larger supporting andcontributing constituents. However, BioTrace Factors 150 displayed insmaller and muted colored icons may draw the attention of the HCP to aconstituent that although not obvious could be a contributor to thepatient's symptoms that may be easily missed. For instance, the patienthas joint pain, they are seemingly healthy, but contracted a microbetraveling abroad which may cause leaky gut which could be associatedwith joint pain and nausea. A recent travel icon 202, although smallwithin the display, may point to an alternative diagnosis.

The color of the correlated BioTrace Factors 150 may allow an HCP toquickly determine the significance of BioTrace Factors 150 that areknown to highly correlate with the exhibited symptoms and largelycontribute to diagnosis. As an example, primary colors may present thissignificance. In the example above, the bright yellow icon 202indicating that the patient may possibly have a leaky gut caused byingestion of a microbe is easily identified in a primary color causing aphysician to take interest in a less common BioTrace Factor 150 that hasa high correlation of Factor Impact 156. Factor Impact 156 can increasein correlation based on duration of symptom, timing of possibleingestion of microbe, type of microbe, known symptoms that areexhibited, travel to certain areas and other BioTrace Factors 150. ThePMD 10 provides for indicators to be tied to time blocks to visuallyprovide the time and duration of BioTrace Factors 150 that may becritical to proper diagnosis. The BioTraceIT Application 62 furtherprovides a correlation of BioTrace Factors 150 that have a lowcorrelation with symptoms and are not commonly known to influencepatient perception. These low correlation BioTrace Factors 150 may bepresented as muted colors. A color ring or border 204 indicator aroundan icon may represent a factor that has the potential to affect aphysiological sensor reading in this instance pain as in this examplewhere stress in a muted colored ring 206 may be a BioTrace Factor 150that can increase perception of pain and therefore the patient'sexpressed pain may be augmented and not a clear indicator of the degreeof the physical problem. The BioTraceIT Application 62 visuallyrepresents using the color, size, and shape indicators to allow an HCPto investigate correlations further to improve the diagnosis and overalltreatment of the patient. The PMD 10 further provides reference links tomedical journals, and patient data within one environment to assist inhaving an HCP arrive at a well-supported diagnosis and treatment plan asquickly as possible. As shown in FIG. 20, a comparison of BioTraceFactors 150 may provide for a physician to determine appropriate testsas derived from the statistical analysis and correlation of BioTraceFactors 150 completed by the BioTraceIT Application 62. A testingprotocol may be presented as a different shape such as a triangle toindicate the significance of the correlation and that further tests maypossibly provide a more complete diagnosis. The BioTraceIT Application62 provides for each icon to be selected to present patient data relatedto the BioTrace Factors 150, i.e. weight tracked over time for obesity,compared with tracked outcome measures, e.g. decrease in pain over time.The statistical relevance of any BioTrace Factor 150 and/or whattreatments were used; and related research and treatment protocolsapproved by the clinic or institution may be provided and may also bepresented in dialog boxes 210, pull down menus, and/or through links 212that open the other components and features of the PMD 10, relatedpatient information with those applications, or to open documents orother data resources. The significance of the color, shape and size oficons may also be provided in an icon description dialog box 214.

In this example, the OBESITY icon 200 shown as a larger icon may be acommon factor in patients experiencing joint pain. However, Patient A216 is suffering from TMD and therefore extra weight would not beresponsible for excessive stress on temporomandibular joints. Therefore,while the OBESITY icon 200 may be almost as large as the STRESS icon 190it is in a MUTED COLOR due to a lower correlation between this BioTraceFactor 150 and the patient's TMD related symptoms. However, the STRESSicon 200 may be slightly less prevalent in the general population andtherefore have a smaller size compared to OBESITY icon 200 and be in asecondary color due to lesser relevance among the general population.Stress may cause physical activity, such as teeth grinding that canaggravate and cause TMD. Additionally, stress can increase a patient'spain experience which may increase their symptoms. For this reason, inPatient B 218 while stress is a muted color it has a PRIMARY COLOR RINGwhich denotes that this BioTrace Factor 150 affects the physiologicalreadings in this case of pain.

The SPORTS INJURY icon 198 represents an even smaller population but canhave significant correlation in the diagnosis of both Patient A 216 andPatient B 218 examples as both knee pain and TMD can be caused by aprior sports injury. For example, if Patient A was playing hockey andwas hit in the jaw with a hockey stick this injury may have a highercorrelation depending on the nature of the injury. Targeting eachBioTrace Factor 150 from each individual whether it be physiological andsocial in nature such as stress, or physical in nature such as a priorinjury combined with associated physiological readings associated withthe PainTrace data and other data acquired from other sensors leads to agreater understanding of the effectiveness and tracking of treatmentoutcomes. Furthermore, the duration of pain, if untreated and chronic ormaladaptive in nature, can increase the perception of pain, known ashyperalgesia, hence the darker hued COLOR RING to denote the FactorImpact of a sports injury on perception of symptoms. The bright color ofthe FEMALE AGE 30 icon 220 for Patient A 216, indicates that TMD is mostcommon in females age 20-40. This age group is less relevant for kneepain so the icon 221 is a MUTED COLOR. From the correlation presented inthe BioTraceIT Application, an OSTEOARTHRITIS TEST TRIANGLE 222indicates that the BioTrace Factors 150 may support a diagnosis ofosteoarthritis as significant where ˜14% suffer osteoarthritis by theage of 24 and after age 65 the incidence rises to 35%. Due to the age ofthe patient this would be a more relevant factor in an elderly patient.Since the patient is age 30 this BioTrace Factors 150 represents a smallpopulation however if they suffer from osteoarthritis this would havesignificant relevance. There is no evidence of osteoarthritis buttesting/imaging as indicated by the testing triangle 222 to rule outarthritis may be valid. Understanding contributing BioTrace Factors 150and relevance, and tracking treatment outcomes using the PainTracesensor data and data from other sensors, may lead to potentially moreeffective and expeditious diagnosis and treatment resulting in improvedhealth, shorter times to return to work and daily activities, and asubsequent reduction in healthcare spending due to improved treatmentsresulting in faster recoveries and a decrease in lost work days whichfurther positively impacts the economy.

Through the BioTraceIT Application correlation and analysis, whichrevolves around pain as a central symptom to evaluate and diagnoseillness, disease state, health, and healing, an HCP might recommendweight loss and target one or more BioTrace Factors 150 that may besignificant to diagnosis and treatment. Subsequent patient visits, datafrom the PainTrace Application 70 and LifeTraceIT data would allow theHCP to track selected target factors with the BioTraceIT Application 62providing visual comparisons showing time span, duration and effect ofactions and treatments taken by the patient based on physiologicalreadings and logged activity gathered to evaluate effectiveness oftreatments and interventions which can further be transformed into aBioTrace Progress Score 280 which provides a cumulative score based onall criteria for quick reference and simple tracking of outcomes. Asshown in FIG. 21, the software would automatically track and graphprogress and relate patient information, such as weight loss, andcorrelate with improvement in symptom. The target factors may be relatedto the Pain Trace Factor 102 that provides an indication of increases ordecreases in pain. The weight 224 of the person may be tracked andvisually displayed. The time block 78 may represent any acceptable scalesuch as weeks or months to display changes in the targeted BioTraceFactor 150. A comparison of the data over time or with respect todifferent patients or populations may support strategies for moreeffective results. While exercise is well known to contribute to thereduction of weight, presenting a third BioTrace Factor 150 of exercise226 over a time period and resulting weight loss as well as painreduction, is an important correlation that may be effective to make apatient change their behavior. A summary 228 and BioTrace FactorAnalysis 230 may also be accessible through the BioTraceIT Application62. The BioTraceIT Application 62 would provide statistical significanceof correlation to improved outcome; provide average improvements over aperiod of time, such as patient lost five pounds per week over atwo-month period, where using LifeTraceIT software eating patterns andfood choices could additionally be correlated to improvements as well asevaluation of targeted patient engagement and the impact on behaviorchange and decision making. Positive impact individual patient activityand decision making would contribute to an increase in a positiveBioTrace Progress Score 280. Decreases in use of medication andsubsequent cost savings would then be tracked for use by the MediTraceITcomponent 64 of the PMD 10. The BioTrace Progress Score 280 can be usedas a metric for both the BioTraceIT software and the MediTraceITsoftware applications within the PMD 10. The BioTrace Factor 150 datamay further be analyzed for subsequent software updates to PMD 10 forimproved objective measurements and factor impact algorithms.

End-users may also view data without using icons and review in a typicalspreadsheet and bar graph format. Whether viewing in a visual or agraphical format, a user can click on each BioTrace Factor 150, FactorImpact 156 or Contribution Factor 162 for explanation of relevance,resources, related studies, treatment protocols, and correlated patientdata as well as other information to assist and support effectivediagnosis and treatment. If an institution chooses they may link thisdata to the MediTraceIT component 64 of the PMD 10 and through anintegration with their electronic medical records be provided withrepresentations of BioTraceIT Progress Scores 280 reflecting outcomesshowing improvement over subsequent patient visits to show efficacy oftreatment, review how subsequent interventions are related to initialsymptoms and treatment, and additionally review the healthcare costsrelated to treatment. As shown in FIG. 22, the MediTraceIT component 64may provide a dashboard interface 240 that provides for the user as anHCP, physician, administrator or others to select patient data within aPatient Link module 242, review actions taken related to the patient'shealth care within a Health Care Provider (HCP) module 244 and analyzetreatments with respect to costs within a Cost Analysis Module 246. ThePatient Link module 242 provides access to components and features inthe PMD 10 related to the patient's BioTrace Factors 150, the patient'ssymptoms 250, the patient's PainTrace data 252, and access to Surveys254 of the patient that may provide status of the patient's currenthealth. The HCP module 244 may provide access to information ondetermined Diagnosis 256, Treatments 258, and Prescriptions 260 that mayalso provide access to allergies 262 or drug interaction 264information. The MediTraceIT component 64 may further provide access toa Demographic module 266 for treatments and cost comparisons presentedfor patients having similar BioTrace Factors 150 and BioTraceIT ProgressScores 280 a Reference module 268 to provide information on acute andchronic disease states. Each of these modules of the MediTraceITcomponent 64 of the PMD 10 may provide detailed information about thepatient and the patient's diagnosis and treatment to allow a user toverify and validate steps taken by the HCPs and physicians in treatingthe patient.

The Cost Analysis Module 246 provides costs associated with the stepstaken in Treatments 270, Medications 272, Tests 274, and Hospital Visits276. The costs information 280 may be restricted using administrativetools that set access levels and permissions based on the user. However,the MediTraceIT application 64 may be targeted to the physician andhealthcare provider using LifeTraceIT 60 and BioTraceIT 62 and the painmeasurement data to track treatment outcomes in order to present thecost benefits realized from successful outcomes. By tracking treatmentoutcomes, positive results are reinforced based on the patient'swillingness and adherence to the requirements of the treatment resultingin costs benefits which may be returned to the patient in the form ofinsurance discounts for example. Costs benefits are further realized byhaving a physician more quickly identify ineffective treatments and/orto remedy misuse of medication by a patient. Using MediTraceIT 64 withthe outcome tracking of BioTraceIT 62 and physiological readings of thePainTrace data, healthcare costs may directly correlate treatment withobjective measures of improved outcomes as evidenced by decreased painlevels for the patient. This comprehensive approach using the componentsof the PMD 10 provides improved diagnostic analysis, validation oftreatments and the realization of cost benefits within an easilyaccessible software application that correlates and presents data in auseful and effective way for patients, HCPs and physicians.

Example 1

The measurement of pain matrix activity using the PainTrace device 14 ofthe PMD 10 is shown before and after acupuncture treatment in FIG. 23.Prior to treatment a mean pain level of 9.4 mV in a patient having lowback pain was recorded. The patient self-reported a VAS value of four(4) prior to treatment. After treatment, the mean pain level decreased,represented by a positive reading of 6.4 mV and the patientself-reported a VAS value of zero (0). Using the PMD, a change in painmatrix activity was observed indicating a successful response totreatment. Furthermore, a quantitative measure of “health” as describedas a degree of no pain is available.

Example 2

In FIG. 24, a patient having an axillary nerve injury was examined todetermine shoulder pain and healing progression. During the seven (7)minute reading, over 395 seconds, the patient self-reported an initialVAS value of zero (0) during the initial 40 second recorded baselineperiod. At 40 seconds the shoulder was externally rotated, noted as anoxious stimulus, to exasperate the axillary nerve injury and generatepain. Pain matrix activity increased as measured using the PainTracedevice of the PMD as indicated by the deflection from the baseline to areading of approximately −5; reflecting an increase in pain. Insubsequent shoulder rotations stimulating a pain response at 200 secondand at 290 seconds, the pain matrix activity as measured by thePainTrace device 14 correlated with the self-reported VAS values. A VASvalue was not recorded, during the initial noxious stimulus at 40seconds. An extrapolated value was added for graphical purposes that isequivalent to the subsequent VAS scores and corresponding measurement bythe PainTrace device 14 as indicated by the diamonds and matching trendand inflection points of the measured PainTrace data. Correlating thisdata with BioTrace Factors 150 including patient populations using thePMD demonstrates a quantitative measure of pain matrix activity andreal-time monitoring.

Example 3

In FIG. 25, a horse diagnosed with laminitis was measured using thePainTrace device 14 of the PMD 10 prior to nerve resection surgery toalleviate pain to the affected foot, and exhibited a −22 in deflectionfrom a zero baseline pre-surgery. Two days after surgery painmeasurements were taken and a −45 deflection was shown. After 10 days ofrecovery the pain matrix activity had decreased to a −5 deflection. Bythe eighteenth day post-op, the readings increased to +9 and horseexhibited a pain-free post-surgical status. On day twenty-five, thehorse was allowed out of its stall for the first time post-surgery andpain matrix activity registered a level of +4 which as a deflection fromthe +9 readings denotes some pain, or a level of fatigue, in the animal.After six months of recovery, PainTrace device 14 measurements weretaken and the horse exhibited the same non-pain readings of +9 and wasdiagnosed by a veterinarian to have fully recovered from surgery.

Example 4

As shown in FIG. 26, in a twenty (20) person study of lower back painpatients receiving acupuncture treatment, the PainTrace device 14 of thePMD was used to measure and monitor pain matrix activity before andafter treatment over five (5) consecutive outpatient visits. In 18 ofthe 20 cases, treatment resulted in decreased pain measurement levelswith results ranging in deflection values from 1.0 to 13.0. In Subjects10 and 11 there was a negative deflection of the PainTrace device 14measurement indicating more pain post-treatment compared topre-treatment values. Further investigation of the Subject 11 revealedthat the subject had fallen during the visit and was experiencing boththe pre-existing back pain and recent leg pain simultaneously.Acupuncture treatment was performed specifically for the lower back, andhad minimal effect on the other injury. The PainTrace device 14accurately detected continued pain in the subject and providedinformation on successful treatment outcomes for the other individualswithin the study. Although the present invention has been described insome detail by way of illustration and example for purposes of clarityand understanding it will, of course, be understood that various changesand modifications may be made in the form, details, and arrangementswithout departing from the scope of the invention.

What is claimed is:
 1. An autonomic function monitoring device,comprising: a pain matrix activity measurement device having a pluralityof sensors configured to be positioned contralaterally at similarlocations on the left and right side of the body, the sensors comprisinga pressure measurement device configured to measure the pressure of asensor against the skin; the pain matrix activity measurement deviceconfigured to acquire data from the contralateral sensors, thecontralateral sensors configured to measure pain matrix activity; a dataacquisition system configured to acquire pain matrix activity data fromthe pain matrix activity measurement device, the data acquisition systemcomprising a non-transitory computer readable medium within a network ofcentral processing units having memory and data storage and havingembodied thereon one or more computer programs causing one or more ofthe central processing units to execute certain steps of; accessingpressure data from a pressure measurement device and displaying anindicator or marker of the pressure measurement to allow for adjustmentto have the sensors configured to be placed contralaterally have equalpressure against the skin; accessing data from the plurality of sensors;and identifying deflections from the data accessed from the plurality ofsensors configured to be positioned contralaterally at similar locationson the left and right side of the body as measurements of pain matrixactivity providing a quantitative measure of pain that is used todetermine the levels of a patient's pain and health.
 2. The autonomicfunction monitoring device of claim 1 wherein the one or more centralprocessing units is further configured to determine a delta from thepoint in time of a deflection to the maximum amount of deflection, thedelta providing the quantitative measure of pain from the measurementsof pain matrix activity from the plurality of sensors configured to bepositioned contralaterally at similar locations on the left and rightside of the body, the delta configured to a numerical rating scalecorrelated to a numerical rating scale used for the self-reporting ofpain.
 3. The autonomic function monitoring device of claim 1 wherein thepain matrix activity measurement device is configured to acquire datafrom the plurality of sensors configured to be positionedcontralaterally at similar locations on the left and right side of thebody for measurements of pain matrix activity without applying a voltageto the sensors.
 4. The autonomic function monitoring device of claim 1wherein the pain matrix activity measurement device configured toacquire data from the plurality of sensors configured to be positionedcontralaterally at similar locations on the left and right side of thebody for measurements of pain matrix activity with applying a voltage tothe sensors.
 5. The autonomic function monitoring device of claim 1wherein the pain matrix activity measurement device is configured toacquire data from the plurality of sensors configured to be positionedcontralaterally at similar locations on the left and right side of thebody by applying a float current to the sensors intermittently.
 6. Theautonomic function monitoring device of claim 1 wherein the pressuremeasurement device of the sensors is configured to be placedcontralaterally on the skin having a strain gauge configured to measurethe pressure of a sensor against the skin.
 7. The autonomic functionmonitoring device of claim 1 wherein sensors of the plurality of sensorsare two pairs configured to be placed ipsilaterally, the first pair ofipsilateral sensors configured to be placed contralaterally from thesecond pair of ipsilateral sensors; and the autonomic functionmonitoring device configured to measure skin conductivity between thefirst pair of ipsilateral sensors; the autonomic function monitoringdevice configured to measure skin conductivity between the second pairof ipsilateral sensors; the autonomic function monitoring deviceconfigured to determine differences in skin conductivity between thefirst pair of ipsilateral sensors and the second pair of ipsilateralsensors; the autonomic function monitoring device configured to apply avoltage offset for differences within a tolerance level; and provide anindicator of a faulty sensor or limited contact for difference outsideof the tolerance level.
 8. The autonomic function monitoring device ofclaim 1 wherein the pain matrix activity measurement device having aload resistor having resistance of between 0.5k ohms and 900k ohms. 9.The autonomic function monitoring device of claim 8 wherein the loadresistor is a variable resistor configured to incrementally increaseresistance and the pain matrix activity measurement device configured toapply voltage to generate a linear resistance curve and using the linearresistance curve, the adjustment of the variable resistor is configuredto produce maximum current flow.
 10. The autonomic function monitoringdevice of claim 1 comprising a noxious stimulus caliper configured toapply a consistent and repeatable amount of pressure for a consistentperiod of time; and the pain matrix activity measurement deviceconfigured to measure the applied stimulus using the noxious stimuluscaliper to generate a baseline of pain tolerance.
 11. The autonomicfunction monitoring device of claim 1 comprising a motion detector. 12.The autonomic function monitoring device of claim 1 comprising a heartrate monitor.
 13. The autonomic function monitoring device of claim 1comprising a heart rate variability monitor.
 14. The autonomic functionmonitoring device of claim 1 comprising a blood pressure monitor. 15.The autonomic function monitoring device of claim 1 comprising agalvanic skin response measurement device.
 16. The autonomic functionmonitoring device of claim 1 comprising a skin temperature measurementdevice.
 17. The autonomic function monitoring device of claim 1comprising heart rate monitor, heart rate variability monitor, bloodpressure monitor, galvanic skin response measurement device, temperaturemeasurement device, and motion detector.
 18. The autonomic functionmonitoring device of claim 1 comprising SaaS, PaaS and on demandcomputing services and a shared resource database through a web browseror other interface.
 19. The autonomic function monitoring device ofclaim 1 comprising an electronic circuit for the initialization,identification, location, acquisition, control and communication to aplurality of sensors.
 20. An autonomic function monitoring devicecomprising: a pain matrix activity measurement device having a pluralityof sensors and wherein at least one pair of sensors configured to bepositioned contralaterally at similar locations on the left and rightside of the body; at least one of the plurality of sensors configured tobe placed ipsilaterally on the skin, the plurality of sensors comprisinga pressure measurement device having a strain gauge configured tomeasure the pressure of a sensor against the skin, the pain matrixactivity measurement device configured to provide an indicator or markerof the pressure measurement to allow for adjustment to have the at leastone ipsilaterally sensor have a pressure measurement equal to at leastone other sensor within the plurality of sensors; the pain matrixactivity measurement device configured to acquire data from thecontralateral sensors, the contralateral sensors configured to measurepain matrix activity; a data acquisition system configured to acquirepain matrix activity data from the pain matrix activity measurementdevice, the data acquisition system comprising a non-transitory computerreadable medium within a network of central processing units havingmemory and data storage and having embodied thereon one or more computerprograms causing one or more of the central processing units to executecertain steps of; accessing pressure data from a pressure measurementdevice and displaying an indicator or marker of the pressure measurementto allow for adjustment to have the sensors configured to be placedcontralaterally have equal pressure against the skin; accessing datafrom the plurality of sensors; and identifying deflections from the dataaccessed from the plurality of sensors configured to be positionedcontralaterally at similar locations on the left and right side of thebody as measurements of pain matrix activity providing a quantitativemeasure of pain that is used to determine the levels of a patient's painand health.